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1.
Braz. j. biol ; 84: e249617, 2024. graf
Article in English | LILACS, VETINDEX | ID: biblio-1345540

ABSTRACT

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.


Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou "teiú". Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.


Subject(s)
Animals , Hibernation , Lizards , Oxidation-Reduction , Oxidative Stress , Erythrocytes
2.
Braz. j. biol ; 84: e254010, 2024. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1345561

ABSTRACT

Abstract The impact of fish oil concentration on the oxidative stability of microcapsules through the spray drying process using chitosan and maltodextrin as wall material was studied. Emulsions were prepared with different Tuna fish oil (TFO) content (TFO-10%, TFO20%, TF030% TF0-40%) while wall material concentration was kept constant. Microencapsulated powder resulting from emulsion prepared with high fish oil load have high moisture content, wettability, total oil and low encapsulation efficiency, hygroscopicity and bulk tapped density. Oxidative stability was evaluated periodically by placing microcapsules at room temperature. Microcapsules prepared with TFO-10% presented high oxidative stability in terms of peroxide value (2.94±0.04) and anisidine value (1.54±0.02) after 30 days of storage. It was concluded that optimal amounts of fish oil for microencapsulation are 10% and 20% using chitosan and maltodextrin that extended its shelf life during study period.


Resumo Foi estudado o impacto da concentração de óleo de peixe na estabilidade oxidativa de microcápsulas por meio do processo de secagem por atomização, utilizando quitosana e maltodextrina como material de parede. As emulsões foram preparadas com diferentes teores de óleo de atum (TFO) (TFO-10%, TFO20%, TF030% TF0-40%), enquanto a concentração de material de parede foi mantida constante. O pó microencapsulado resultante da emulsão preparada com alta carga de óleo de peixe tem alto teor de umidade, molhabilidade e óleo total e baixa eficiência de encapsulação, higroscopicidade e densidade extraída a granel. A estabilidade oxidativa foi avaliada periodicamente colocando microcápsulas à temperatura ambiente. As microcápsulas preparadas com TFO-10% apresentaram alta estabilidade oxidativa em termos de valor de peróxido (2,94 ± 0,04) e valor de anisidina (1,54 ± 0,02) após 30 dias de armazenamento. Concluiu-se que as quantidades ideais de óleo de peixe para microencapsulação são de 10% e 20% usando quitosana e maltodextrina que prolongaram sua vida útil durante o período de estudo.


Subject(s)
Animals , Fish Oils , Chitosan , Powders , Tuna , Oxidative Stress
3.
Braz. j. biol ; 83: e247360, 2023. tab
Article in English | LILACS, VETINDEX | ID: biblio-1350301

ABSTRACT

Abstract Excessive intake of non-steroidal anti-inflammatory drugs such as, diclofenac sodium (DS) may lead to toxicity in the rats. In this work, we aimed to examine the protective impact of lentil extract (LE) and folic acid (FA) on the hematological markers, the kidney tissue oxidative stress and the renal function against diclofenac sodium (DS) in male albino rats. The rats (120-150 g) were divided into four equal groups randomly, the first group kept as the untreated control. The second group was administrated with DS (11.6 mg/kg b.wt. orally once/day). The third group was received DS+FA (11.6 mg/kg b.wt.+76.9 microgram/kg b.wt.) orally once/day. The fourth group was treated with DS+LE (11.6 mg/kg b.wt.+500 mg/kg b.wt.) orally once/day. After four weeks, the results revealed that DS produced a significant decrease in the values of red blood cells (RBCs), hemoglobin concentration (Hb), hematocrit (HCT) and white blood cells (WBCs). On the other hand, there was a significant increase in the platelets count. Also, DS induced a renal deterioration; this was evidenced by the significant increase in the serum levels of urea, creatinine, uric acid, Na, Ca, Mg as well as the nitric oxide (NO) level in the kidney tissue. Also, there were a significant reduction in the serum levels of potassium (K) and reduced glutathione (GSH) in the kidney homogenates. Moreover, the findings in the rats treated by DS+LE or DS+FA showed a potential protection on the hematological markers, oxidative stress in the kidney tissue and the renal function disturbed by DS. LE and FA could play a potent role for the prevention the adverse hematological, the kidney tissue oxidative stress and the renal dysfunction caused by DS via their anti-oxidative and bioactive phytochemicals.


Resumo A ingestão excessiva de anti-inflamatórios não esteroidais, como o diclofenaco de sódio (DS), pode causar toxicidade em ratos. Neste trabalho, objetivamos examinar o impacto protetor do extrato de lentilha (LE) e ácido fólico (AF) em marcadores hematológicos, no estresse oxidativo do tecido renal e na função renal contra o diclofenaco de sódio (DS) em ratos albinos machos. Os ratos (120-150 g) foram divididos em quatro grupos iguais aleatoriamente, sendo o primeiro grupo mantido como controle não tratado. O segundo grupo foi administrado com DS (11,6 mg / kg de peso corporal por via oral uma vez / dia). O terceiro grupo recebeu DS + FA (76,9 mg / kg de peso corporal por via oral uma vez / dia). O quarto grupo foi tratado com DS + LE (500 mg / kg de peso corporal por via oral uma vez / dia). Após quatro semanas, os resultados revelaram que o DS produziu uma diminuição significativa nos valores de glóbulos vermelhos (RBCs), concentração de hemoglobina (Hb), hematócrito (HCT) e glóbulos brancos (WBCs). Por outro lado, houve um aumento significativo na contagem de plaquetas. Além disso, o DS induziu uma deterioração renal; isso foi evidenciado pelo aumento significativo dos níveis séricos de ureia, creatinina, ácido úrico, Na, Ca, Mg e também do nível de óxido nítrico no tecido renal. Além disso, houve uma redução significativa nos níveis séricos de potássio (K) e glutationa reduzida (GSH) nos homogenatos renais. Além disso, os achados nos ratos tratados com DS + LE ou DS + FA mostraram uma proteção potencial sobre os marcadores hematológicos, estresse oxidativo no tecido renal e função renal perturbada pelo DS. LE e AF podem desempenhar um papel potente na prevenção do estresse hematológico adverso, do estresse oxidativo do tecido renal e da disfunção renal causada pelo DS por meio de seus fitoquímicos antioxidantes e bioativos.


Subject(s)
Animals , Rats , Diclofenac/toxicity , Lens Plant , Plant Extracts/pharmacology , Oxidative Stress , Folic Acid , Antioxidants
4.
Arch. latinoam. nutr ; 72(3): 205-217, sept. 2022. ilus, tab, graf
Article in Spanish | LILACS, LIVECS | ID: biblio-1399287

ABSTRACT

Las catequinas del té verde (Camellia sinensis) (CTV) presentan efectos benéficos para la salud asociados a su potencial antioxidante. Por otra parte, el estrés oxidante es una de las vías de inducción de daño genotóxico. De ahí que, en la presente revisión se realizó un análisis de los efectos antigenotóxicos y genotóxicos de las CTV, haciendo énfasis en las vías implicadas en estos procesos y sus efectos en la salud. Se realizó una revisión de artículos indexados en las bases de datos de PubMed® y Science Direct® (2021) con las palabras clave "green tea" y "green tea catechins". Se delimitaron los estudios utilizando los operadores booleanos "AND", "OR" y "NOT" ("antigenotoxic", "genotoxic", "antioxidant" y "prooxidant"). En su mayoría se consideraron las publicaciones del 2016 al 2021. Se observó que los efectos benéficos en la salud de las CTV están relacionados con: a) su actividad antioxidante mediante la captura, inhibición y prevención de la formación de las especies reactivas de oxígeno; b) la regulación del sistema antioxidante endógeno; c) la activación de los mecanismos de reparación al contribuir en la eliminación del aducto 8-hidroxi-2'-desoxiguanosina; d) la inducción de apoptosis en células con daño al ADN; y e) la inhibición de la inflamación relacionada con su actividad antiapoptótica. Si bien, en algunos de los estudios se reportaron efectos genotóxicos, estos a su vez contribuyeron en la eliminación de células con daño genético, por lo que, no se puede considerar del todo a la actividad genotóxica de las CTV como perjudiciales para la salud(AU)


The green tea catechins (Camellia sinensis) (CTV) have beneficial effects for health associated with their antioxidant potential. Moreover, oxidative stress is one of the pathways for inducing genotoxic damage. Hence, in this review, an analysis of the antigenotoxic and genotoxic effects of CTV was carried out, emphasizing the pathways involved in these processes and their effects on health. A review of articles indexed in the PubMed® and ScienceDirect® (2021) databases with the keywords "green tea" and "green tea catechins" was carried out. Studies were delimited using the Boolean operators "AND", "OR" and "NOT" ("antigenotoxic", "genotoxic", "antioxidant" and "prooxidant"). For the most part, publications from 2016 to 2021 were considered. It was observed that the beneficial health effects of CTVs are related to: a) their antioxidant activity through the capture, inhibition and prevention of the formation of reactive oxygen species; b) the regulation of the endogenous antioxidant system; c) the activation of the repair mechanisms by contributing to the elimination of the 8-hydroxy-2'-deoxyguanosine adduct; d) the induction of apoptosis in cells with DNA damage; and e) the inhibition of inflammation related to its antiapoptotic activity. Although some of the studies reported genotoxic effects, these in turn contributed to the elimination of cells with genetic damage. Therefore, the genotoxic activity of CTV cannot be considered as harmful to health


Subject(s)
Tea , Catechin/analysis , Oxidative Stress , Publications , Cells , PubMed , Antioxidants
5.
Arch. argent. pediatr ; 120(3): 174-179, junio 2022. tab
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1368143

ABSTRACT

Introducción. La exposición ambiental a plomo (Pb) aún constituye un problema de salud pública, particularmente para los niños. El estrés oxidativo podría representar un mecanismo primario asociado a su toxicidad. El objetivo del presente estudio fue determinar los niveles de Pb en sangre (Pb-S) en niños de 1 a 6 años de La Plata y alrededores con exposición ambiental, y su relación con biomarcadores de estrés oxidativo. Población y métodos. Estudio analítico de corte transversal. Se evaluaron niños clínicamente sanos de 1 a 6 años. Se determinaron los niveles de Pb-S, las actividades de enzimas antioxidantes y el grado de peroxidación lipídica. Se utilizó el paquete estadístico R versión 3.5.1. Resultados. Participaron 131 niños, mediana de edad 2,33 años. La media geométrica de los niveles de Pb-S fue 1,90 µg/dL; el 32 % presentó plombemias cuantificables y el 3 %, niveles ≥5 µg/dL (referencia internacional). Al comparar los biomarcadores de estrés oxidativo según los niveles de Pb-S, solo se observó diferencia significativa entre las medianas de las sustancias reactivas al ácido tiobarbitúrico (TBARS): 12,0 versus 10,0 nmol MDA/mL plasma; p = 0,02. Asimismo, la correlación entre las plombemias y las TBARS fue positiva (r = 0,24; p = 0,012). Conclusiones. La mayoría de los niños mostraron niveles de Pb-S menores a los límites recomendados por agencias internacionales, que si bien, no producen alteraciones en la actividad de enzimas antioxidantes, sí inducen peroxidación lipídica. Estos resultados reflejan la utilidad de este biomarcador como una herramienta diagnóstica temprana para evaluar los efectos subtóxicos del Pb.


Introduction. Environmental exposure to lead is still a major public health problem, especially in children. Oxidative stress may be a primary mechanism associated with toxicity. Theobjective of this study was to measure blood lead levels (BLLs) in children aged 1 to 6 years expos to lead in La Plata and suburban areas and their relation to oxidative stress biomarkers. Population and methods. Cross-sectional,analytical study. Clinically healthy children aged1 to 6 years were analyzed. BLLs, antioxidant enzyme activity, and extent of lipid peroxidation were measured. The statistical softwarepackage R, version 3.5.1, was used. Results. A total of 131 children participated; their median age was 2.33 years. The geometric mean of BLLs was 1.90 µg/dL; 32% showed a measurable BLL and 3%, BLLs ≥ 5 µg/dL (international reference). The comparison ofoxidative stress biomarkers based on BLshowed a significant difference in median thiobarbituric acid reactive substances (TBARS):12.0 versus 10.0 nmol MDA/mL of plasma;p = 0.02. In addition, the correlation between BLLs and TBARS was positive (r = 0.24; p = 0.012 Conclusions. Most children had a BLL below the limit recommended by international agencies; although such BLLs do not affantioxidant enzyme activity, they can induce lipid peroxidation. These results demonstrate theusefulness of this biomarker as an early diagnosistool to assess subtoxic lead effects.


Subject(s)
Humans , Infant , Child, Preschool , Child , Lead/analysis , Lead Poisoning/diagnosis , Argentina , Biomarkers , Cross-Sectional Studies , Thiobarbituric Acid Reactive Substances , Oxidative Stress , Environmental Exposure/adverse effects , Antioxidants
6.
Int. j. morphol ; 40(3): 697-705, jun. 2022. ilus, tab
Article in English | LILACS-Express | LILACS | ID: biblio-1385688

ABSTRACT

SUMMARY: An association between certain food additives and chronic diseases is reported. Current study determined whether administering toxic doses of the food additive monosodium glutamate (MSG) into rats can induce aortopathy in association with the oxidative stress and inflammatory biomarkers upregulation and whether the effects of MSG overdose can be inhibited by vitamin E. MSG at a dose of (4 mg/kg; orally) that exceeds the average human daily consumption by 1000x was administered daily for 7 days to the rats in the model group. Whereas, rats treated with vitamin E were divided into two groups and given daily doses of MSG plus 100 mg/ kg vitamin E or MSG plus 300 mg/kg vitamin E. On the eighth day, all rats were culled. Using light and electron microscopy examinations, a profound aortic injury in the model group was observed demonstrated by damaged endothelial layer, degenerated smooth muscle cells (SMC) with vacuoles and condensed nuclei, vacuolated cytoplasm, disrupted plasma membrane, interrupted internal elastic lamina, clumped chromatin, and damaged actin and myosin filaments. Vitamin E significantly protected aorta tissue and cells as well as inhibited MSG-induced tissue malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). The highest used vitamin E dosage was more effective. Additionally, a significant correlation was observed between the aortic injury degree and tissue MDA, TNF-α, IL-6, and superoxide dismutase (SOD) levels (p=0.001). Vitamin E effectively protects against aortopathy induced by toxic doses of MSG in rats and inhibits oxidative stress and inflammation.


RESUMEN: Se reporta una asociación entre ciertos aditivos alimentarios y enfermedades crónicas. El objetivo de este estudio fue determinar si la administración de dosis tóxicas del aditivo alimentario glutamato monosódico (MSG) en ratas puede inducir aortopatía en asociación con el estrés oxidativo y la regulación positiva de los biomarcadores inflamatorios y si el efecto de una sobredosis de MSG se puede inhibir con vitamina E. Se administró MSG diariamente durante 7 días una dosis de (4 g/kg; por vía oral) que excede el consumo diario humano promedio, en 1000x a las ratas del grupo modelo. Mientras que las ratas tratadas con vitamina E se dividieron en dos grupos y se administraron dosis diarias de MSG más 100 mg/kg de vitamina E o MSG más 300 mg/kg de vitamina E. Todas las ratas fueron sacrificadas en el octavo día. Usando exámenes de microscopía óptica y electrónica, se observó una lesión aórtica profunda en el grupo modelo demostrada por una capa endotelial dañada, células musculares lisas degeneradas (SMC) con vacuolas y núcleos condensados, citoplasma vacuolado, membrana plasmática rota, lámina elástica interna interrumpida, cromatina agrupada y filamentos de actina y miosina dañados. La vitamina E protegió significativamente el tejido y las células de la aorta, además de inhibir el malondialdehído tisular (MDA) inducido por MSG, la interleucina-6 (IL-6) y el factor de necrosis tumoral alfa (TNF-α). La dosis más alta de vitamina E utilizada fue más efectiva. Además, se observó una correlación significativa entre el grado de lesión aórtica y los niveles tisulares de MDA, TNF-α, IL-6 y superóxido dismutasa (SOD) (p=0,001). La vitamina E efectivamente protege contra la aortopatía inducida por dosis tóxicas de MSG en ratas e inhibe el estrés oxidativo y la inflamación.


Subject(s)
Animals , Rats , Aorta/drug effects , Aortic Diseases/chemically induced , Sodium Glutamate/toxicity , Vitamin E/pharmacology , Aorta/pathology , Sodium Glutamate/administration & dosage , Vitamin E/administration & dosage , Microscopy, Electron , Interleukin-6/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Rats, Sprague-Dawley , Oxidative Stress/drug effects , Disease Models, Animal , Malondialdehyde/antagonists & inhibitors
7.
Int. j. morphol ; 40(3): 781-788, jun. 2022. ilus
Article in English | LILACS-Express | LILACS | ID: biblio-1385681

ABSTRACT

SUMMARY: High-intensity physical exercises can cause oxidative stress and muscle damage. Several medicinal plants have been used as antioxidant and anti-inflammatory agents. The present study evaluated high-intensity resistance exercise (HIRE) associated with Schinus Terebentifholius ethanolic extract (EE) on oxidative parameters and muscle damage in Wistar rats. Animals were divided into 04 groups (n=10/group): 1. Control (CG) - animals that did not undergo HIRE and were treated with vehicle (distilled water, orally); 2. Acute exercise (AE) - animals submitted to acute exercise session; 3. Exercise + vehicle (EV) - animals that underwent HIRE and were treated with vehicle and 4. Exercise + extract (EX) animals administered with Schinus terebenthifolius EE (100mg/Kg, orally) and submitted to the exercise session. Schinus terebenthifolius EE showed high in vitro antioxidant activity (13.88 ± 0.36 mg/mL). Before the experimental period, lactate was measured at pre and post moments of AE (p<0.0001) and EX (p<0.0001) groups. After the acute session, the following were evaluated: oxidative stress {malondialdehyde (MDA), sulfhydryl groups (SH) and ferric reducing antioxidant power (FRAP)}, muscle damage (creatine kinase (CK) and lactate dehydrogenase (LDH)), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the in vivo analyses of the EX group compared to AE and EV groups, respectively: hepatic (MDA: p<0.0001 and SH: p=0.0033, in both; FRAP: p=0.0011 and p=0.0047), muscle (MDA, SH and FRAP: p<0.0001, in both; CK: p=0.0001 and p<0.0001; LDH: p<0.0001, in both), serum levels (MDA: p=0.0003, p=0.0012, SH: p=0.0056, p=0.0200, FRAP: p=0.0017 and p=0.0165) were significant. There was no significant difference in ALT and AST markers. It could be concluded that Schinus terebenthifolius EE associated with HIRE attenuated oxidative stress and muscle damage in rats.


RESUMEN: Los ejercicios físicos de alta intensidad pueden causar estrés oxidativo y daño muscular. Varias plantas medicinales se han utilizado como agentes antioxidantes y antiinflamatorios. El presente estudio evaluó el ejercicio de resistencia de alta intensidad (HIRE) asociado con el extracto etanólico (EE) de Schinus terebentifholius sobre los parámetros oxidativos y el daño muscular en ratas Wistar. Los animales se dividieron en 4 grupos (n=10/grupo): 1. Control (GC) - animales que no se sometieron a HIRE y fueron tratados con vehículo (agua destilada, por vía oral); 2. Ejercicio agudo (AE) - animales sometidos a sesión de ejercicio agudo; 3. Ejercicio + vehículo (EV) - animales que se sometieron a HIRE y fueron tratados con vehículo y 4. Ejercicio + extracto (EX) animales administrados con Schinus terebenthifolius EE (100 mg/kg, por vía oral) y sometidos a la sesión de ejercicio. Schinus terebenthifolius EE mostró una alta actividad antioxidante in vitro (13,88 ± 0,36 mg/mL). Antes del período experimental, se midió el lactato en los momentos pre y post de los grupos AE (p<0,0001) y EX (p<0,0001). Tras la sesión aguda, se evaluaron: el estrés oxidativo malondialdehído (MDA), grupos sulfhidrilo (SH) y poder antioxidante reductor férrico (FRAP), daño muscular (creatina quinasa (CK) y lactato deshidrogenasa (LDH)), alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). En los análisis in vivo del grupo EX frente a los grupos AE y EV, respectivamente: hepático (MDA: p<0,0001 y SH: p=0,0033, en ambos; FRAP: p=0,0011 y p=0,0047), muscular (MDA, SH y FRAP: p<0,0001, en ambos; CK: p=0,0001 y p<0,0001; LDH: p<0,0001, en ambos), niveles séricos (MDA: p=0,0003, p=0,0012, SH: p=0,0056, p=0,0200, FRAP: p=0,0017 y p=0,0165) fueron significativas. No hubo diferencia significativa en los marcadores ALT y AST. Se podría concluir que Schinus terebenthifolius EE asociado con HIRE atenuó el estrés oxidativo y el daño muscular en ratas.


Subject(s)
Animals , Rats , Plant Extracts/administration & dosage , Exercise , Anacardiaceae , Antioxidants/administration & dosage , Physical Endurance , Plants, Medicinal , Plant Extracts/pharmacology , Biomarkers , Rats, Wistar , Oxidative Stress , Dietary Supplements , Antioxidants/pharmacology
8.
Säo Paulo med. j ; 140(3): 390-397, May-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1377390

ABSTRACT

ABSTRACT BACKGROUND: Reduced antioxidant defenses may reflect a poor protective response against oxidative stress and this may be implicated in progression of gestational diabetes mellitus (GDM). Oxidative stress induced by hyperglycemia plays a major role in micro and macrovascular complications, which imply endothelial dysfunction. OBJECTIVE: Our aim in this study was to investigate the association between GDM and oxidative stress markers measured in plasma, with regard to revealing changes to total antioxidant capacity (TAC) and total oxidant status (TOS) among mothers showing impairments in oral glucose tolerance tests (OGTTs). DESIGN AND SETTING: Prospective study at a university hospital in Turkey. METHODS: The study group consisted of 50 mothers with GDM, and 59 healthy mothers served as controls. Umbilical cord blood samples were taken from all mothers during delivery and breast milk samples on the fifth day after delivery. TAC, TOS, thiol and disulfide levels were measured. RESULTS: No statistically significant relationship between the blood and milk samples could be found. An analysis on correlations between TAC, TOS and certain parameters revealed that there were negative correlations between TOS and total thiol (r = -0.386; P < 0.001) and between TOS and disulfide (r = -0.388; P < 0.001) in milk in the control group. However, these findings were not observed in the study group. CONCLUSION: Our findings suggested that a compensatory mechanism of oxidative stress was expected to be present in gestational diabetes mellitus and that this might be ameliorated through good glycemic regulation and antioxidant supplementation.


Subject(s)
Humans , Animals , Female , Pregnancy , Diabetes, Gestational , Sulfhydryl Compounds/analysis , Prospective Studies , Oxidative Stress/physiology , Milk/metabolism , Milk/chemistry , Disulfides/analysis , Fetal Blood/metabolism , Fetal Blood/chemistry , Antioxidants/analysis
9.
An. Fac. Cienc. Méd. (Asunción) ; 55(1): 27-38, 20220401.
Article in Spanish | LILACS, BDNPAR | ID: biblio-1366663

ABSTRACT

Introducción: Procesos como la mutagénesis, la carcinogénesis y la teratogénesis son producto de la interacción de agentes de origen endógeno como exógeno que interactúan con la molécula de ADN en forma crónica produciendo rupturas en la doble hélice, y en cromosomas completos resultando en la inestabilidad genómica. El estrés oxidativo al que se encuentran sometidas las células al formarse las especies reactivas de oxígeno (ROS) y también las especies reactivas de nitrógeno (RNS), que pueden provenir de radicales producidos a consecuencia de la diabetes o en estados iniciales de la enfermedad renal crónica o como respuesta a procesos inflamatorios en estados avanzados de estas patologías, actúan como agentes genotóxicos endógenos.Objetivos: Esta investigación tuvo como objetivo determinar el daño basal en la molécula de ADN de pacientes diabéticos hemodializados, a través del ensayo del Cometa, como un bioindicador de inestabilidad genómica., durante seis meses de tratamiento. Materiales y métodos: Se planteó un estudio longitudinal prospectivo de cohorte para comparar los diferentes niveles de daño antes y durante los primeros seis del tratamiento de hemodiálisis. Se evaluó con el test del cometa o electroforesis de células individuales, el daño basal en muestras de sangre venosa de pacientes diagnosticados con Diabetes de tipo II como control negativo y en pacientes diabéticos con enfermedad renal crónica antes de iniciar el tratamiento de diálisis y luego durante el tratamiento. Se utilizó el test de t- Student para muestras independientes y emparejadas. Resultados: Se observó un aumento significativo de daño basal y oxidativo en el material genético de pacientes diabéticos con enfermedad renal crónica, comparados con los controles negativos (p< 0.005) y se observó, además, que el daño celular aumenta con el tratamiento de hemodiálisis (p<0.005). Conclusión: Los resultados obtenidos en esta investigación permiten concluir que el estrés oxidativo tiene un efecto genotóxico y que el nivel de daño genético es un buen bioindicador del avance de la enfermedad renal crónica y que la hemodiálisis induce a un aumento de daño a nivel del material genético, aumentando el riesgo de carcinogénesis.


Introduction: Processes such as mutagenesis, carcinogenesis and teratogenesis are the product of the interaction of agents of endogenous and exogenous origin that interact with the DNA molecule in a chronic way producing ruptures in the double helix, and in complete chromosomes resulting in genomic instability. The oxidative stress to which the cells are subjected when reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed, which may come from radicals produced as a result of diabetes or in initial stages of chronic kidney disease or in response to inflammatory processes in advanced stages of these pathologies, act as endogenous genotoxic agents. Objectives: This research aimed to determine the basal damage in the DNA molecule of hemodialyzed diabetic patients, through the Comet assay, as a bioindicator of genomic instability, during six months of treatment. Materials and methods: For this research, a prospective longitudinal cohort study was proposed to compare the different levels of genetic damage before and during the first six of hemodialysis treatment. Baseline damage was evaluated with the comet test or single cell electrophoresis, in venous blood samples from patients diagnosed with Type II Diabetes as a negative control and in diabetic patients with chronic kidney disease before starting dialysis treatment and then during treatment. Results: A significant increase in basal and oxidative damage was observed in the genetic material of diabetic patients with chronic kidney disease, compared to negative controls (p< 0.005) and it was also observed that cell damage increases with hemodialysis treatment (p<0.005). The t-Student test was used for independent and paired samples. Conclusion: The results obtained in this research allow us to conclude that oxidative stress has a genotoxic effect and that the level of genetic damage is a good bioindicator of the progression of chronic kidney disease and that hemodialysis induces an increase in damage at the level of the genetic material, increasing the risk of carcinogenesis.


Subject(s)
Renal Dialysis , Comet Assay , Dialysis , Research , DNA , Oxidative Stress
10.
Bol. latinoam. Caribe plantas med. aromát ; 21(2): 256-267, mar. 2022. tab, ilus
Article in English | LILACS | ID: biblio-1395304

ABSTRACT

Gentamicin induced acute nephrotoxicity (GIAN) is considered as one of the important causes of acute renal failure. In recent years' great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of GIAN. Hence, the current study was designed to investigate the effect of green coffee bean extract (GCBE) on GIAN in rats. Results of the present study showed that rat groups that received oral GCBE for 7 days after induction of GIAN(by a daily intraperitoneal injection of gentamicin for 7days), reported a significant improvement in renal functions tests when compared to the GIAN model groups. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE-treated groups when compared to GIAN model group. These results indicate that GCBE has a potential role in ameliorating renal damage involved in GIAN.


La nefrotoxicidad aguda inducida por gentamicina (GIAN) se considera una de las causas importantes de insuficiencia renal aguda. En los últimos años, el gran esfuerzo se ha centrado en la introducción de la medicina herbal como un nuevo agente terapéutico para la prevención de GIAN. Por lo tanto, el estudio actual fue diseñado para investigar el efecto del extracto de grano de café verde (GCBE) sobre la GIAN en ratas. Los resultados del presente estudio mostraron que los grupos de ratas que recibieron GCBE oral durante 7 días después de la inducción de GIAN (mediante una inyección intraperitoneal diaria de gentamicina durante 7 días), informaron una mejora significativa en las pruebas de función renal en comparación con los grupos del modelo GIAN. Además, hubo una mejora significativa en los marcadores de estrés oxidativo renal (malondialdehído renal, superóxido dismutasa renal) y cambios histopatológicos renales en los grupos tratados con GCBE en comparación con el grupo del modelo GIAN. Estos resultados indican que GCBE tiene un papel potencial en la mejora del daño renal involucrado en GIAN.


Subject(s)
Animals , Male , Rats , Plant Extracts/administration & dosage , Gentamicins/toxicity , Coffea/chemistry , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Antioxidants/administration & dosage , Superoxide Dismutase/analysis , Plant Extracts/pharmacology , Rats, Wistar , Coffee , Oxidative Stress/drug effects , Kidney/drug effects , Kidney/pathology , Kidney Function Tests , Malondialdehyde/analysis , Antioxidants/pharmacology
11.
Int. j. cardiovasc. sci. (Impr.) ; 35(2): 214-219, Mar.-Apr. 2022. tab
Article in English | LILACS | ID: biblio-1364976

ABSTRACT

Abstract Background Various studies are ongoing related to the radioprotective agents. Herbal preparations are currently becoming popular because of their beneficial effects with fewer side effects compared to the synthetic/semi-synthetic medicines, and Nigella sativa oil (NSO) is only one of them. Objective To investigate NSO for its antioxidant effects on the heart tissue of rats exposed to ionizing radiation (IR). Methods Thirty six male albino Wistar rats, divided into four groups, were designated to group I (IR plus NSO group) that received both 5 Gray of gamma IR to total cranium and NSO; group II (IR alone group) that received IR plus saline, group III (control group of NSO) that received saline and did not receive NSO or IR; group IV (control group) that received only sham IR. Alterations in Total antioxidant status (TAS) and Total oxidant status (TOS), Oxidative stres index (OSI), Sulhydryl group (SH), Lipid hydroperoxide (LOOH), Paraoxonase (PON) levels, Arylesterase (ARE) and Ceruloplasmin (CER) activities in homogenized heart tissue of rats were measured by biochemical methods. Results In heart tissue of the rats in the IR alone group (group II) LOOH, TOS and OSI levels were found to be higher, ARE activity and TAS level were found to be lower than all of the other groups (p < 0.01). These results also support that IR increases oxidative stress and NSO's protective effect. Conclusion NSO would reduce the oxidative damage in the irradiated heart tissue in the experimental rat model.


Subject(s)
Animals , Male , Rats , Radiation-Protective Agents/therapeutic use , Plant Oils/therapeutic use , Nigella sativa , Oxidative Stress/drug effects , Heart/radiation effects , Antioxidants/therapeutic use , Plants, Medicinal , Radiation-Protective Agents/analysis , Rats, Inbred Strains , Rats, Wistar , Oxidative Stress/radiation effects , Plant Preparations/therapeutic use , Cardiotoxicity/drug therapy , Heart/drug effects , Phytotherapy
12.
Braz. J. Vet. Res. Anim. Sci. (Online) ; 59: e188941, fev. 2022. ilus
Article in English | LILACS, VETINDEX | ID: biblio-1380208

ABSTRACT

Canine Distemper is a disease caused by Canine morbillivirus (CM), a pantropic virus that can affect the central nervous system (CNS), causing demyelination. However, the pathogenesis of this lesion remains to be clarified. Brain samples of 14 naturally infected dogs by CM were analyzed to evaluate the presence of oxidative stress and demyelination. RT-PCR assay was performed to confirm a diagnosis of canine distemper in the brain, immunohistochemistry anti-CM was used to localize the viral proteins in the tissue, and anti-4-hydroxy-2-nonenal (4-HNE) was a marker of a product of lipid peroxidation. The results showed the presence of viral proteins in the demyelinated area with the presence of 4-HNE. Our results suggest that the CM virus infection causes oxidative stress leading to lipid peroxidation, which causes tissue damage and demyelination. In conclusion, oxidative stress plays a significant role in canine distemper pathogenesis in the CNS.(AU)


A cinomose canina é uma doença causada pelo Morbilivírus canino (CM), um vírus pantrópico que pode afetar o sistema nervoso central (SNC), causando desmielinização. No entanto, a patogênese dessa lesão não está totalmente esclarecida. RT-PCR e imuno-histoquímica foram realizadas para confirmação do diagnóstico de cinomose em amostras de encéfalo de 14 cães naturalmente infectados. Após confirmação, foi realizada uma avaliação do estresse oxidativo por imuno-histoquímica com uso de anti-4-hidroxi-nonenal (4HNE) como marcador de produtos resultantes da peroxidação lipídica. Os resultados sugerem que a infecção pelo CM causa estresse oxidativo no tecido, levando a peroxidação lipídica, a qual causa danos ao tecido, culminando com desmielinização. Conclui-se que o estresse oxidativo tem papel importante na patogênese da cinomose canina no sistema nervoso central.(AU)


Subject(s)
Animals , Biomarkers/metabolism , Central Nervous System Infections/veterinary , Distemper/diagnosis , Dogs/virology , Immunohistochemistry/instrumentation , Lipid Peroxidation/drug effects , Demyelinating Diseases/veterinary , Morbillivirus/pathogenicity , Oxidative Stress/physiology , Reverse Transcriptase Polymerase Chain Reaction/instrumentation , Cerebrum/virology
13.
Alerta (San Salvador) ; 5(1): 64-73, ene. 28, 2022. tab
Article in Spanish | LILACS, BISSAL | ID: biblio-1354468

ABSTRACT

Los trastornos hipertensivos asociados al embarazo constituyen uno de los síndromes de mayor interés a escala mundial, cerca de 600 000 mujeres mueren anualmente por causas relacionadas. La Organización Mundial de la Salud considera que la incidencia de preeclampsia es siete veces mayor en los países en vías de desarrollo en comparación a los industrializados (2,8 % y 0,4 %, respectivamente). El estrés oxidativo es una de las principales causas asociadas a la preeclampsia, cuyo diagnóstico y manejo adecuado y oportuno son medidas eficaces para disminuir la tasa de morbimortalidad, por lo que diversos autores se han centrado en la búsqueda de biomarcadores predictores de estrés oxidativo entre los cuales encontramos: especies reactivas del ácido tiobarbitúrico, superóxido, catalasa, superóxido dismutasa y glutatión peroxidasa. El presente trabajo describe los principales biomarcadores de estrés oxidativo estudiados mediante la técnica espectrofotométrica debido a que es económica, rápida y precisa


Hypertensive disorders associated with pregnancy are one of the syndromes of greatest interest worldwide, nearly 600,000 women die annually from related causes. The World Health Organization considers that the incidence of preeclampsia is seven times higher in developing countries compared to industrialized ones (2.8% and 0.4%, respectively). Oxidative stress is one of the main causes associated with preeclampsia, whose proper and timely diagnosis and management are effective measures to reduce the morbidity and mortality rate, which is why various authors have focused on the search for predictive biomarkers of oxidative stress among which we find: reactive species of thiobarbituric acid, superoxide, catalase, superoxide dismutase and glutathione peroxidase. The present work describes the main biomarkers of oxidative stress studied by means of the spectrophotometric technique because it is cheap, fast and precise


Subject(s)
Patients , Pre-Eclampsia , Spectrophotometry , Women , Oxidative Stress , Indicators of Morbidity and Mortality , Morbidity , Methods
14.
Int. braz. j. urol ; 48(1): 131-156, Jan.-Feb. 2022. tab, graf
Article in English | LILACS | ID: biblio-1356297

ABSTRACT

ABSTRACT Purpose: Sperm DNA fragmentation (SDF) and seminal oxidative stress are emerging measurable factors in male factor infertility, which interventions could potentially reduce. We evaluated (i) the impact of lifestyle changes combined with oral antioxidant intake on sperm DNA fragmentation index (DFI) and static oxidation-reduction potential (sORP), and (ii) the correlation between DFI and sORP. Materials and Methods: We conducted a prospective study involving 93 infertile males with a history of failed IVF/ICSI. Ten healthy male volunteers served as controls. Semen analysis was carried out according to 2010 WHO manual, whereas seminal sORP was measured using the MiOXSYS platform. SDF was assessed by sperm chromatin structure assay. Participants with DFI >15% underwent a three-month lifestyle intervention program, primarily based on diet and exercise, combined with oral antioxidant therapy using multivitamins, coenzyme Q10, omega-3, and oligo-elements. We assessed changes in semen parameters, DFI, and sORP, and compared DFI results to those of volunteers obtained two weeks apart. Spearman rank correlation tests were computed for sORP and DFI results. Results: Thirty-eight (40.8%) patients had DFI >15%, of whom 31 participated in the intervention program. A significant decrease in median DFI from 25.8% to 18.0% was seen after the intervention (P <0.0001). The mean DFI decrease was 7.2% (95% CI: 4.8-9.5%; P <0.0001), whereas it was 0.42% (95%CI; -4.8 to 5.6%) in volunteers (P <0.00001). No differences were observed in sperm parameters and sORP. Based on paired sORP and DFI data from 86 patients, no correlation was observed between sORP and DFI values (rho=0.03). Conclusion: A 3-month lifestyle intervention program combined with antioxidant therapy reduced DFI in infertile men with elevated SDF and a history of failed IVF/ICSI. A personalized lifestyle and antioxidant intervention could improve fertility of subfertile couples through a reduction in DFI, albeit controlled trials evaluating reproductive outcomes are needed before firm conclusions can be made. Trial registration number and date: clinicaltrials.gov NCT03898752, April 2, 2019.


Subject(s)
Humans , Male , Infertility, Male/drug therapy , Antioxidants/metabolism , Antioxidants/therapeutic use , Spermatozoa , Fertilization in Vitro , Pilot Projects , Prospective Studies , Oxidative Stress , DNA Fragmentation , Life Style
15.
Acta sci., Health sci ; 44: e58558, Jan. 14, 2022.
Article in English | LILACS | ID: biblio-1367771

ABSTRACT

Cardiovascular disease(CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects.This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard foodand receiving by gavage virgin olive oil (HCD+VOO) and(4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low­Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High­Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.


Subject(s)
Animals , Rats , Oxidative Stress/immunology , Atherosclerosis/diet therapy , Diet, High-Fat/methods , Olive Oil/pharmacology , Triglycerides/pharmacology , Lipid Peroxidation/immunology , Cholesterol/pharmacology , Rats, Wistar/immunology , Diet, Atherogenic/methods , Glutathione/pharmacology , Hypercholesterolemia/immunology , Lipoproteins/immunology
16.
Acta sci., Health sci ; 44: e55845, Jan. 14, 2022.
Article in English | LILACS | ID: biblio-1366721

ABSTRACT

The effects of the aqueous extract of Ilex paraguariensis (Ip)and the flavonoid quercetin were tested during the induction of in vivomyocardial ischemia/ reperfusion in Rattus norvegicus. The antioxidant power of the extract and quercetin were chemically determined. The experimental groups were: control, ischemia/reperfusion induction, Iporal treatment, Iporal treatment and ischemia /reperfusion, quercetin oral treatment, and quercetin oral treatment and ischemia/reperfusion. Rats were anesthetized with sodium thiopental and xylazine via intraperitoneal injection and subsequently underwent 15 minutes of ischemia followed by 15 minutes of reperfusion. Ischemia was promoted by tying the left anterior descending coronary artery. Areas of risk and infarction were stained by intravenous Evans blue and triphenyl tetrazolium chloride. Reactive oxygen species (ROS), antioxidant capacity against peroxylradicals, and lipid peroxidation of the myocardium were quantified. A significant reduction in areas of risk and infarction was detected in the ischemic myocardium treated with Ipand quercetin; ROS generation and lipid peroxidation were significantly reduced, and the antioxidant capacity was elevated. Oral administration of Ippromoted antioxidant benefits in the myocardium during ischemia and reperfusion, which reduced infarction. We suggest that Mate (a hot drink made from steeped dried leaves of Ip) consumption is a potential cardioprotective habit of indigenous people from southern South American countries, which must be better understood scientifically and ethnographically.


Subject(s)
Animals , Rats , Flavonoids , Ilex paraguariensis/adverse effects , Ischemia/drug therapy , Antioxidants , Quercetin/analysis , Rats , Reperfusion , Administration, Oral , Oxidative Stress/drug effects , Teas, Medicinal/adverse effects , Myocardial Infarction/drug therapy
17.
São Paulo; s.n; s.n; 2022. 86 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1378701

ABSTRACT

Responsável por milhões de óbitos anuais e um grande custo para a saúde pública, o câncer é a segunda maior causa de mortes no mundo. Dentre seus diversos tipos, o câncer de pulmão, além da alta incidência, é um dos mais letais. A exposição a substâncias tóxicas provenientes da combustão de matéria orgânica, assim como o consumo de cigarro, são os principais responsáveis pela alta incidência de câncer de pulmão. Dentre estas substâncias, está o benzo[α]pireno (B[α]P), um carcinógeno completo, ou seja, capaz de iniciar e promover o processo de carcinogênese. Resultados anteriores obtidos pelo grupo demonstraram que células BEAS-2B expostas a 1 µM de B[α]P apresentaram alterações das concentrações de metabólitos intracelulares, indução de estresse redox e hipermetilação do DNA. A exposição a 1 µM de nicotinamida ribosídeo (NR), um dos precursores de NAD+, foi capaz de proteger as células BEAS-2B contra a transformação induzida por B[α]P, além de impedir totalmente que células não expostas a B[α]P formassem colônias em soft-agar. A utilização da proteômica neste trabalho permitiu verificar a abundância das proteínas nos quatro diferentes grupos de exposição: Controle, B[α]P, B[α]P + NR e NR. Após 120 h de exposição as células foram coletadas, as proteínas extraídas e preparadas para análise. Foram descobertas 3024 proteínas posteriormente analisadas com o objetivo de elucidar vias possivelmente envolvidas na proteção contra o processo de transfomação maligna. Os grupos NR e Controle demonstram ser mais parecidos em relação ao seu conteúdo, enquanto os grupos B[α]P e B[α]P + NR foram mais semelhantes entre si. A análise de proteínas exclusivas revelou menos processos relacionados ao reparo de DNA no grupo tratado apenas com B[α]P quando comparado com B[α]P + NR. A análise estatística do total de proteínas utilizando o teste ANOVA (p < 0,05, N = 5) revelou 564 proteínas diferencialmente expressas entre os grupos. A clusterização nos permitiu observar a diferença na abundância de proteínas entre os quatro tratamentos. As proteínas estão envolvidas em funções como a regulação do metabolismo, resposta a estresse, transdução de sinal, regulação de expressão gênica e morte celular. Um dos clusters (cluster 1), contendo 59 proteínas, revelou poucos processos na análise de enriquecimento, mas as proteínas contidas nele apresentam funções como controle da divisão celular, apoptose e proteção ao estresse redox. Nele podemos observar que, no geral, o tratamento com B[α]P aumentou a abundância de algumas proteínas, o que foi revertido no grupo B[α]P + NR. O tratamento apenas com NR diminuiu a abundância das proteínas contidas nesse cluster. Outro cluster (cluster 4) apresentou 51 proteínas de abundância diminuída durante a exposição ao B[α]P, o que se reverteu no grupo B[α]P + NR. As proteínas desse cluster estão envolvidas em etapas importantes da via glicolítica, de crescimento, adesão, migração e invasão celular. Apesar de ser descrito que a exposição a NR pode aumentar a eficiência do reparo de DNA, os resultados apresentados nesse trabalho indicam que o efeito protetor pode estar relacionado com a modulação do ciclo celular ou alterações na adesão celular


Responsible for millions of annual deaths and a great health expense, cancer is the second leading cause of death in the world. Among its many types, lung cancer, besides its high incidence, is also one of the most lethal. Exposure to toxic substances resulting from the combustion of organic matter, as well as cigarette consumption, are the mainly responsible for the high incidence of lung cancer. One of these substances is benzo[α]pyrene (B[α]P), a complete carcinogen, able to initiate and promote the carcinogenesis process. Results obtained previously demonstrated that BEAS-2B cells exposed to 1 µM BaP presented alterations in the levels of intracellular metabolites, induction of oxidative stress, and hypermethylation of DNA. The exposure to 1 µM nicotinamide riboside (NR), one of the precursors of NAD+, was able to protect BEAS-2B cells against the transformation induced by B[α]P, moreover, it also totally prevented the colonies formation on soft agar in cells not exposed to B[α]P. The use of proteomics allowed us to verify the abundance of proteins in the four different exposure groups: Control, B[α]P, B[α]P + NR e NR. After 120h of exposure, the cells were collected followed by the extraction of the proteins. A total of 3024 proteins were identified and analyzed aiming to elucidate possible pathways involved in the protective effect against the malignant transformation induced by B[α]P. The NR and Control groups showed to be more similar, while B[α]P and B[α]P + NR were more similar. The analysis of exclusive proteins revealed fewer processes related to DNA repair in B[α]P when compared with B[α]P + NR. The statistical analysis of the total proteins using the ANOVA test (p <0.5, N = 5) revealed 564 proteins differentially expressed between the groups. The heatmap showed the difference in protein abundance between the four treatments. Proteins are involved in functionssuch asthe regulation of metabolism, stress response, signal transduction, regulation of gene expression, and cell death. One of the clusters (cluster 1), containing 59 proteins, revealed a few processes in the enrichment analysis, but the proteins contained in it have functions such as control of cell division, apoptosis, and protection from redox stress. It is possible to observe, in general, treatment with B[α]P increased the abundance of some proteins, which was partially reversed in group B[α]P + NR. On the other hand, the NR treatment decreased the abundance of proteins contained in this cluster. Another cluster (cluster 4) showed 51 proteins of decreased abundance during exposure to B [α] P, which was partially reversed in group B[α]P + NR. The proteins in this cluster are involved in important stages of the glycolytic pathway, also in growth, adhesion, migration, and cell invasion. Although it has been described that exposure to NR can increase the efficiency of DNA repair, the results presented in this work indicate that the protective effect may be related to the modulation of the cell cycle or cell adehsion modifications


Subject(s)
Proteomics/classification , Tobacco Products/classification , Carcinogenesis , Neoplasms , Cells/classification , Analysis of Variance , Data Interpretation, Statistical , Cell Death , Niacinamide/agonists , Oxidative Stress , Lung Neoplasms/pathology
18.
São Paulo; s.n; s.n; 2022. 130 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1396955

ABSTRACT

O câncer colorretal (CCR) é o terceiro câncer mais diagnosticado em humanos. O CCR causou mais de 900.000 mortes em 2020 e foi estimado, para o período entre 2020 - 2025, um incremento de 13.5 % no número de casos novos de acordo com a plataforma Web Global Cancer Observatory. A Terapia Fotodinâmica (PDT) é uma alternativa terapêutica promissora. Conhecer as vias de sinalização de morte celular, assim como, as respostas associadas com a resistência ao dano foto-oxidativo, são relevantes para incrementar a eficiência da PDT. Neste trabalho, investigamos como as células de adenocarcinoma colorretal HT 29 respondem ao dano fotoinduzido gerado pelo fotossensibilizador (FS) meso-tetrafenilporfirina dissulfônado (TPPS2a), uma molécula que é ativada pela irradiação com luz em 522 nm. Como esperado, após irradiação (2.1 J cm-2) foi verificado que com o incremento do TPPS2a houve diminuição da viabilidade celular. A concentração do FS escolhida para darmos seguimento ao estudo foi a necessária para reduzir em 30 % a sobrevida celular (DL30; 148 nM). Abordagens moleculares nos permitiram identificar que nas células fotossensibilizadas a redução na maturação da catepsina D (CTSD, 55 %) e da catepsina B (CTSB, 52 %) contribuem com a disfunção endolisossomal. Além disso, comprovamos que as células fotossensibilizadas tiveram, pela menor quantidade de CTSD ativa, o processamento da prosaposina (PSAP) significativamente afetado. Células coletadas após 24 horas de irradiação expressaram 7 vezes mais PSAP do que as amostras dos grupos controle, sugerindo que as reações de oxidação causadas pelo TPPS2a podem ocasionar o acúmulo de glicoesfingolipídios nos endossomos e nos lisossomos, mimetizando o fenótipo observado em doenças de armazenamento lisossomal. Imagens de células HT 29 com expressão estável da proteína LGALS3 fusionada ao marcador EFGP mostraram que, após 24 horas de irradiação, as células não ativaram a lisofagia para remover os endossomos e os lisossomos danificados. A ausência do recrutamento da LGALS3 também apontou que as membranas dos endossomos e dos lisossomos não apresentam rupturas permanentes que permitam a passagem de uma molécula de 26 kDa. Experimentos complementares de análise da expressão proteica dos marcadores autofágicos LC3-II e p62/SQSTM1 (referida como p62) confirmaram o bloqueio do fluxo autofágico nas células fotosenssibilizadas. Pelo envolvimento do sistema endolisossomal no tráfego de membranas e no fluxo de lipídios, o aumento da transcrição da Hidroximetilglutaril-CoA reductase (HMGCR) (≈ 1.6 vezes) uma enzima envolvida na síntese de novo do colesterol - sugeriu que a disfunção dos endossomos e dos lisossomos altera a distribuição de colesterol. Não obstante, para manter a homeostase lipídica nas células fotossensibilizadas este não foi o único mecanismocompensatório acionado, uma vez que houve um incremento sutil; porém, significativo (1.2 vezes) na transcrição da ceramidase ácida (ASAH1). Em conjunto, nossos dados apontam que a fotossensibilização com TPPS2a constitui uma ferramenta promissora para causar dano no sistema endolisossomal, inibindo a autofagia e permitindo o estudo das respostas metabólicas em células expostas a estresse oxidativo


Colorectal cancer (CRC) is the third most commonly diagnosed cancer in humans. CRC caused more than 900,000 deaths in 2020 and it was estimated for the period 2020 - 2025, an increase of 13.5 % in the number of new cases according to the Global Cancer Observatory Web platform. Photodynamic Therapy (PDT) is a promising therapeutic alternative. Understandings of cell death signaling pathways as well as the adaptive responses associated with resistance to photo-oxidative damage are relevant to optimize the effectiveness of PDT. For this purpose, in this research, we investigated how HT-29 colorectal adenocarcinoma cells respond to photosensitization reactions generated by TPPS2a, a molecule activated by irradiation with light at 522 nm. PS concentrations displayed increased inhibitory effect on cell viability after irradiation (2.1 J cm-2). The lethal dose selected to photosensibilize cells was the TPPS2a concentration able to reduce 30 % of cell survival (LD30; 148 nM). By molecular methods, we observed a reduction in cathepsin D (CTSD, 55 %) and cathepsin B (CTSB, 52 %) maturation, depletion that may contribute to endo-lysosomal dysfunction in photosensitized cells. It is widely known that endo-lysosomal cathepsins are crucial in protein turnover and degradation. Thus, we focused on the consequence of CTSD reduction. Literature data indicate that CTSD plays a key role in prosaposin (PSAP) processing to the four saposins (SAPs) that are required in glycosphingolipids breakdown. In fact, our results in photosensitized cells showed that, due to the lower amount of active CTSD, PSAP processing was significantly affected. Cells collected after irradiation expressed 7 times more PSAP than cells from the control groups. This data suggest that oxidative photodamage induced by TPPS2a may result in glycosphingolipid-accumulating endosomes and lysosomes, phenotype which mimics lysosomal storage diseases. Furthermore, we monitored by fluorescence microscopy a form of selective autophagy which detects and removes damaged endosomes and lysosomes known as lysophagy. Images of HT-29 cells expressing Galectin 3/LGALS3 fused to EFGP showed that photosensitized cells did not activate lysophagy. The absence of LGALS3 recruitment also indicated that the membranes of endosomes and lysosomes do not present ruptures which allow the passage of proteins with a molecular weight up to at least 26 kDa. Protein expression analysis of the autophagic markers LC3-II and p62/SQSTM1 (referred as p62) confirmed autophagic flux blockade in cells challenged with photoactivated TPPS2a. The endo-lysosomal system plays a key role in membrane trafficking and lipid flux. At the transcriptional level, 1.6-fold increase in gene expression of Hydroxymethylglutaryl-CoA reductase (HMGCR) - an enzyme involved in the synthesis de novo of cholesterol - indicated that endosomes and lysosomes dysfunction alters the distribution of cholesterol in cellschallenged with photoactivated TPPS2a. However, to maintain lipid homeostasis in photosensitized cells, this was not the only compensatory mechanism triggered, since there was a slightly increase (1.2-fold) in the transcription of acid ceramidase (ASAH1). Taken together, our data showed that photosensitization with TPPS2a constitutes a promising tool to damage the endolysosomal system, to inhibit autophagy and to study metabolic responses in cells exposed to oxidative stress


Subject(s)
Autophagy , Colorectal Neoplasms/pathology , Cathepsins/chemistry , Photochemotherapy , Gene Expression , Cholesterol/adverse effects , Lysosomal Storage Diseases , Oxidative Stress , HT29 Cells/metabolism
19.
Int. j. morphol ; 40(4): 874-879, 2022. ilus
Article in English | LILACS-Express | LILACS | ID: biblio-1405255

ABSTRACT

SUMMARY: Diabetes and hypertension account for the majority of chronic kidney injury cases that can lead to renal failure. The link between the leukocytes common antigen (CD45) and diabetic kidney disease (DKD) with and without metformin incorporation in an animal model has not been investigated before. Therefore, we sought to assess the extent of leukocytes infiltration into kidney tissues 10 weeks following the induction of diabetes in rats treated with metformin. In addition, we monitored blood and urine parameters associated with diabetes. The model group of rats received streptozotocin (STZ; 50 mg/kg) injection after being fed for 14 days on a high-fat diet (HFD) and continuously fed a HFD until they were culled, at week 12. The protective group was treated in the same way except that these animals were put from day 1 on metformin (200 mg/kg) until being culled, on week 12. Kidneys were immunostained with CD45 as a marker of leukocytes infiltration and examined by light microscopy. Urine samples were tested for urine albumin and collected blood was analyzed for sugar, urea, creatinine, and oxidative stress and antioxidants biomarkers. Kidney injury secondary to diabetes was developed as demonstrated by (i) increased blood glucose, urea, and malondialdehyde (MDA) as a marker of lipid peroxidation; and (ii) kidney tissue damage and marked increase in kidney tissues expressing CD45 positive cells. The above markers were inhibited (p0.0006) by metformin. Also, a significant correlation was observed between CD45 score and glycemia, urea, MDA, and the antioxidant superoxide dismutase (SOD). Thus, our data demonstrate an association between the infiltration of CD45+ inflammatory cells into kidney tissues and biomarkers of kidney damage in a rat model of DKD, which was effectively protected by metformin.


RESUMEN: La diabetes y la hipertensión representan la mayoría de los casos de lesión renal crónica que pueden provocar insuficiencia renal. El vínculo entre el antígeno común de los leucocitos (CD45) y la enfermedad renal diabética (DKD) con y sin incorporación de metformina en un modelo animal no se había anteriormente investigado. El objetivo fue evaluar el grado de infiltración de leucocitos en los tejidos renales 10 semanas después de la inducción de diabetes en ratas tratadas con metformina. Además, monitoreamos los parámetros de sangre y orina asociados con la diabetes. El grupo modelo de ratas recibió una inyección de estreptozotocina (STZ; 50 mg/kg) después de ser alimentadas durante 14 días con una dieta alta en grasas (HFD) y continuamente alimentadas con un HFD hasta que fueron sacrificadas, en la semana 12. El grupo protector fue tratado de la misma manera excepto que estos animales fueron recibieron desde el día 1 metformina (200 mg/kg) hasta ser sacrificados, en la semana 12. Los riñones fueron inmunoteñidos con CD45 como marcador de infiltración de leucocitos y examinados por microscopía óptica. Las muestras de orina se analizaron en busca de albúmina y la sangre recolectada se analizó en busca de glucosa, urea, creatinina y biomarcadores de estrés oxidativo y antioxidantes. La lesión renal secundaria a la diabetes se desarrolló como lo demuestra (i) el aumento de la glucosa en sangre, la urea y el malondialdehído (MDA) como marcador de la peroxidación lipídica; y (ii) daño del tejido renal y marcado aumento en los tejidos renales que expresan células positivas para CD45. Los marcadores anteriores fueron inhibidos (p≤0.0006) por metformina. Además, se observó una correlación significativa entre la puntuación de CD45 y la glucemia, la urea, la MDA y la superóxido dismutasa antioxidante (SOD). Por lo tanto, nuestros datos demuestran una asociación entre la infiltración de células inflamatorias CD45+ en los tejidos renales y biomarcadores de daño renal en un modelo de rata con DKD, que fue protegido de manera efectiva por metformina.


Subject(s)
Animals , Rats , Diabetes Mellitus , Acute Kidney Injury/prevention & control , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Biomarkers , Leukocyte Common Antigens , Oxidative Stress/drug effects , Disease Models, Animal , Hypoglycemic Agents/therapeutic use , Inflammation , Kidney/drug effects , Metformin/therapeutic use
20.
Int. j. morphol ; 40(4): 1060-1066, 2022. ilus, tab
Article in English | LILACS-Express | LILACS | ID: biblio-1405249

ABSTRACT

SUMMARY: N-Acetylcysteine (NAC) is used for contrast induced acut kidney injury (CI-AKI) prophylaxis because of its antioxidant effects. Paricalcitol, which has reno-protective effects, is likely to provide a more effective prophylaxis when added to NAC treatment. The study was designed based on this hypothesis. The study was organised to include 4 groups each consisting of 7 rats. Group 1 was the control group, and Group 2 included rats with CI-AKI. Rats in Group 3 were administered NAC at a dose of 100 mg/kg via oral gavage once a day for 5 days. Rats in group 4 were administered paricalcitol at a dose of 0.4 mcg/kg once a day for 5 days in addition to NAC. CI-AKI was induced after the treatments in both groups. The study was terminated on the sixth day. Samples were collected from the rats' sera and kidney tissues to study oxidant and antioxidant parameters; kidney function tests were also studied. There were significant differences between the contrast nephropathy group (Group 2) and NAC and NAC+paricalcitol groups with respect to serum urea and creatinine levels. When the same groups were compared regarding oxidant (TOS-MDA) and antioxidant (TAC-Paraoxonase) parameters, we observed that the oxidant parameters increased in serum and kidney tissue samples with NAC use, and that effect was strengthened by the addition of paricalcitol to NAC treatment. However, despite increased antioxidant effectiveness, we observed no decrease in urea and creatinine levels when paricalcitol was added for CI-AKI in rats. There was no significant difference between Group 3 and Group 4. Paricalcitol provides a more potent antioxidant effect in both serum and kidney tissue samples when added to NAC treatment in rats with CI-AKI. Despite increased antioxidant parameters, however, paricalcitol does not provide a significant decrease in urea and creatinine levels.


RESUMEN: Debido a sus efectos atioxidantes la N- acetilcisteína (NAC) se usa para la profilaxis de la lesión renal aguda inducida por contraste (CI-AKI). Es probable que el paricalcitol, que tiene efectos renoprotectores, proporcione una profilaxis más eficaz cuando se agrega al tratamiento con NAC. En base a esta hipótesis el estudio fue diseñado para incluir cuatro grupos cada uno compuesto por siete ratas. El grupo 1 fue el grupo control y el grupo 2 incluyó ratas con CI-AKI. A las ratas del Grupo 3 se les administró NAC con una dosis de 100 mg/kg por sonda oral una vez al día, durante 5 días. A las ratas del grupo 4 se les administró paricalcitol a una dosis de 0,4 mcg/kg una vez al día durante 5 días, además de NAC. Se indujo CI-AKI después de los tratamientos en ambos grupos. El estudio finalizó el sexto día. Se recolectaron muestras de suero y tejidos renales de ratas para estudiar los parámetros oxidantes y antioxidantes; También se estudiaron las pruebas de función renal. Hubo diferencias significativas entre el grupo de nefropatía por contraste (Grupo 2) y los grupos NAC y NAC+paricalcitol con respecto a los niveles séricos de urea y creatinina. Cuando se compararon los mismos grupos con respecto a los parámetros oxidantes (TOS-MDA) y antioxidantes (TAC-Paraoxonase), observamos que los parámetros oxidantes aumentaron en muestras de suero y tejido renal con el uso de NAC, y ese efecto se vio reforzado por la adición de paricalcitol a tratamiento NAC. Sin embargo, a pesar de una mayor eficacia antioxidante, no observamos una disminución en los niveles de urea y creatinina cuando se agregó paricalcitol para CI-AKI en ratas. No hubo diferencias significativas entre el Grupo 3 y el Grupo 4. El paricalcitol proporciona un efecto antioxidante más potente tanto en muestras de suero como de tejido renal cuando se agrega al tratamiento con NAC en ratas con CI-AKI. Sin embargo, a pesar del aumento de los parámetros antioxidantes, el paricalcitol no proporciona una disminución sig- nificativa en los niveles de urea y creatinina.


Subject(s)
Animals , Rats , Acetylcysteine/administration & dosage , Ergocalciferols/administration & dosage , Acute Kidney Injury/prevention & control , Antioxidants/administration & dosage , Acetylcysteine/pharmacology , Ergocalciferols/pharmacology , Rats, Wistar , Oxidative Stress/drug effects , Contrast Media/adverse effects , Acute Kidney Injury/chemically induced , Antioxidants/pharmacology
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