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1.
Int. j. morphol ; 41(5): 1427-1438, oct. 2023.
Article in English | LILACS | ID: biblio-1521021

ABSTRACT

SUMMARY: The main cause of mortality and disability globally is myocardial infarction (MI). Isoproterenol (ISO), a β-adrenoceptor agonist, has been used to induce rat myocardial necrosis. Whereas interleukin-37 (IL-37) has anti-inflammatory and cytoprotective properties. The study aimed to investigate the potential protective effects of IL-37 administration on cardiac architecture, oxidative stress, and inflammatory markers during ISO-induced MI in rats. Three groups of adult male rats were used in this study, the normal control group (n=8), ISO-induced MI group (n=8) that received isoproterenol hydrochloride (ISO) (100 mg/kg/day, SC, for the first 2 consecutive days), and IL-37-treated group (ISO+IL-37) (n=8) that received recombinant human IL-37 (40 µg/kg /day, intraperitoneally, for 2 weeks during and after ISO injections. Heart rate (HR.) and ECG changes were monitored. Some oxidative stress markers such as superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) tissue levels in the tissue homogenate were assayed. Interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), caspase-8, P53, and C- reactive protein (CRP) were among the inflammatory markers examined. In addition, serum levels of creatinine kinase (CK-MB) and lactate dehydrogenase (LDH) were analyzed to evaluate the myocardial injury. For histological analysis, tissues were sectioned, fixed in paraffin, and stained with hematoxylin and eosin (H&E), Masson Trichrome and, immunohistochemical against NF-kB, TNF-α, and Caspase-9. IL-37 improved ECG changes, cardiac enzyme markers, and some inflammatory markers of oxidative stress in ISO-induced MI. It also improved the histopathological and immunohistochemical changes in MI. In conclusion: IL-37 might be a promising therapeutic modality in myocardial infarction.


La principal causa de mortalidad y discapacidad a nivel mundial es el infarto de miocardio (IM). El isoproterenol (ISO), un agonista de los receptores adrenérgicos β, se ha utilizado para inducir necrosis miocárdica en ratas. Mientras que la interleucina-37 (IL-37) tiene propiedades antiinflamatorias y citoprotectoras. El estudio tuvo como objetivo investigar los posibles efectos protectores de la administración de IL-37 en la arquitectura cardíaca, el estrés oxidativo y los marcadores inflamatorios durante el infarto de miocardio inducido por ISO en ratas. En este estudio se utilizaron tres grupos de ratas macho adultas, el grupo control normal (n=8), el grupo con IM inducido por ISO (n=8) que recibió clorhidrato de isoproterenol (ISO) (100 mg/kg/día, SC, durante los primeros 2 días consecutivos) y el grupo tratado con IL-37 (ISO+IL- 37) (n=8) que recibió IL-37 humana recombinante (40 µg/kg/día, por vía intraperitoneal, durante 2 semanas durante y después de las inyecciones de ISO. Se monitorearon la frecuencia cardíaca (FC) y los cambios en el ECG. Se analizaron algunos marcadores de estrés oxidativo como la superóxido dismutasa (SOD), el óxido nítrico (NOx), el malondialdehído (MDA) y los niveles tisulares de glutatión (GSH) en el homogeneizado de tejido. La interleucina-6 (IL-6), el factor de necrosis tumoral-α (TNF-α), la caspasa-8, la P53 y la proteína C reactiva (CRP) se encontraban entre los marcadores inflamatorios examinados. Se analizaron los niveles de creatinoquinasa (CK-MB) y lactato deshidrogenasa (LDH) para evaluar la lesión miocárdica; para el análisis histológico se seccionaron los tejidos, se fijaron en parafina y se tiñeron con hematoxilina y eosina (H&E), Tricromo de Masson e inmunohistoquímica contra NF-kB, TNF-α y Caspasa-9. IL-37 mejoró los cambios de ECG, los marcadores de enzimas cardíacas y algunos marcadores inflamatorios de estrés oxidativo en el IM inducido por ISO. Además mejoró los cambios histopatológicos e inmunohistoquímicos en MI. En conclusión: la IL-37 podría ser una modalidad terapéutica prometedora en el infarto de miocardio.


Subject(s)
Animals , Male , Rats , Interleukins/administration & dosage , Heart/drug effects , Myocardial Infarction/chemically induced , Myocardial Infarction/prevention & control , Immunohistochemistry , Rats, Wistar , Oxidative Stress/drug effects , Inflammation , Isoproterenol/adverse effects
2.
Int. j. morphol ; 41(1): 231-236, feb. 2023. ilus, tab, graf
Article in English | LILACS | ID: biblio-1430516

ABSTRACT

SUMMARY: Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control - S; NADES - N; Doxorubicin - Dox; Carotenoids - Car; CardiofortIN - CF; NADES-Doxorubicin - N-Dox; Carotenoids-Doxorubicin - Car-Dox; CardiofortIN-Doxorubicin - CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.


La doxorrubicina (DOX) es uno de los fármacos necesarios para el tratamiento de los 10 tipos más comunes de cáncer. El principal efecto adverso que limita el uso clínico de DOX es la cardiotoxicidad. Debido a que los datos de la literatura indican un papel protector de los carotenoides en la toxicidad inducida por doxorrubicina, en nuestro estudio comparamos el efecto cardioprotector de una mezcla de carotenoides de calabaza y una preparación antioxidante disponible comercialmente. Los animales se distribuyeron en 8 grupos (Control - S; NADES - N; Doxorrubicina - Dox; Carotenoides - Car; CardiofortIN - CF; NADES-Doxorrubicina - N-Dox; Carotenoides-Doxorrubicina - Car-Dox; CardiofortIN- Doxorrubicina - CF-Dox). Las secciones histológicas se tiñeron con hematoxilina-eosina (HE) y se analizaron para detectar la presencia de daño miocárdico mediante la puntuación de daño por doxorrubicina (DDS). A partir del homogeneizado de tejido cardíaco se determinó la intensidad de la peroxidación lipídica y la actividad enzimática antioxidante específica (superóxido dismutasa, catalasa, glutatión S-transferasa, glutatión peroxidasa). En los grupos Car-DOX y CF-DOX, la peroxidación lipídica se redujo significativamente en comparación con el grupo DOX. El pre tratamiento de los animales con carotenoides y, en menor medida, con CardiofortlN condujo a una mayor actividad de las enzimas antioxidantes, en comparación con el grupo DOX. Al ser pre tratados con carotenoides, solo el 50 % de los animales tenían algún grado de daño miocárdico y ningún animal tenía daño extenso. El pre tratamiento con CardiofortIN mostró un efecto protector menor. El pre tratamiento con extracto de carotenoides redujo significativamente el DDS, por lo que el grupo Car-DOX mostró cambios equivalentes a un daño miocárdico leve. Aunque el pre tratamiento con CardiofortIN redujo los valores de la puntuación DDS, los animales aún tenían un nivel moderado de daño al miocardio. Este estudio in vivo y sus hallazgos indican que los carotenoides extraídos de la calabaza pueden ser un agente cardioprotector prometedor contra la cardiotoxicidad inducida por doxorrubicina, al menos en parte mediada por la inhibición del estrés oxidativo inducido por DOX.


Subject(s)
Animals , Rats , Carotenoids/administration & dosage , Doxorubicin/toxicity , Cucurbita/chemistry , Cardiotoxicity/prevention & control , Cardiotonic Agents , Lipid Peroxidation , Catalase , Rats, Wistar , Oxidative Stress/drug effects , Glutathione Peroxidase , Glutathione Transferase , Antibiotics, Antineoplastic/toxicity , Neoplasms/drug therapy , Antioxidants
3.
Braz. J. Pharm. Sci. (Online) ; 59: e20467, 2023. graf
Article in English | LILACS | ID: biblio-1439510

ABSTRACT

Abstract Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis.


Subject(s)
Epinephrine/agonists , Peripheral Nervous System Diseases/classification , Toxicity , Neurons/classification , Peripheral Nerves/abnormalities , Bromides/antagonists & inhibitors , Oxidative Stress/drug effects , Antioxidants/pharmacology
4.
Acta cir. bras ; 38: e380223, 2023. graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1439114

ABSTRACT

Purpose: To explore the role and mechanism of curcumin (Cur) in reducing oxidative stress damage in rats with nephrolithiasis induced by ethylene glycol (EG). Methods: Thirty male rats were divided into normal control, model, positive (10% potassium citrate), Cur-10 (10 mg/kg curcumin) and Cur-20 (20 mg/kg curcumin) groups. Results: The results of kidney tissue section stained by hematoxylin-eosin and von Kossa showed that curcumin treatment can inhibit the formation of kidney stones. The biochemical test results showed that the urea (Ur), creatinine (Cr), uric acid (UA), inorganic phosphorus and Ca2+ concentrations in urine decreased after being treated with curcumin. There were significant differences between different doses of curcumin (P < 0.05). Compared with the Cur-10 group, Cur-20 had a more significant inhibitory effect on malondialdehyde (MDA) (P < 0.05). In addition, reverse transcription polymerase chain reaction (PCR) detection and immunohistochemical results indicated that the osteopontin (OPN) in the kidney was significantly reduced after curcumin treatment. Conclusion: Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones.


Subject(s)
Animals , Male , Rats , Oxidative Stress/drug effects , Ethylene Glycol/analysis , Curcumin/administration & dosage , Osteopontin/analysis , Nephrolithiasis/veterinary
5.
Braz. j. biol ; 83: 1-6, 2023. tab
Article in English | LILACS, VETINDEX | ID: biblio-1468878

ABSTRACT

Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P<0.01) increased and LPO reduced significantly (P<0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.


O succinato de desvenlafaxina (DVS) inibe seletivamente a recaptação da serotonina e é aprovado para transtornos depressivos maiores. Esta pesquisa investigou a influência do DVS na modulação da monoamina cerebral e do estresse oxidativo em camundongos. O potencial antiepiléptico de DVS (10, 20 ou 30 mg / kg / i.p.) Em pentilenotetrazole (PTZ; 85 mg / kg) com i.p. via de administração, estricnina (STR; 75 mg / kg) com i.p. via, pilocarpina (400 mg / kg) com s.c. rota e convulsão induzida por MES de eletrochoque máximo em modelos de camundongos. As atividades de estresse oxidativo, ou seja, superóxido dismutase (SOD), glutationa (GSH) e peroxidação lipídica (LPO), bem como ácido gama-aminobutírico (GABA) nos cérebros de camundongos convulsivos induzidos por PTZ. O tratamento com DVS aumentou a latência para desenvolver crises e diminuiu a mortalidade em roedores contra convulsões induzidas por PTZ, STR e pilocarpina. Os resultados de siezures conduzidos por MES revelaram que o DVS reduziu significativamente a duração e a mortalidade da extensão tônica dos membros posteriores. Os níveis de cérebro, SOD, GSH e GABA aumentaram significativamente (P < 0,01) e o LPO reduziu significativamente (P < 0,01) após o tratamento com DVS. Além disso, o DVS não apresentou sinais de coordenação motora no teste do rotarod. Demonstramos o papel do DVS na gênese da convulsão em camundongos sob condição de controle e atenua o dano oxidativo induzido por PTZ.


Subject(s)
Male , Animals , Mice , Anticonvulsants/administration & dosage , Seizures/drug therapy , Oxidative Stress/drug effects , Pentylenetetrazole/adverse effects , Desvenlafaxine Succinate/pharmacology , Depressive Disorder/drug therapy , Mice
6.
Braz. j. biol ; 83: 1-9, 2023. graf, tab
Article in English | LILACS, VETINDEX | ID: biblio-1468957

ABSTRACT

Allium cepa L. is a commonly consumed vegetable that belongs to the Amaryllidaceae family and contains nutrients and antioxidants in ample amounts. In spite of the valuable food applications of onion bulb, its peel and outer fleshy layers are generally regarded as waste and exploration of their nutritional and therapeutic potential is still in progress with a very slow progression rate. The present study was designed with the purpose of doing a comparative analysis of the antioxidant potential of two parts of Allium cepa, i.g., bulb (edible part) and outer fleshy layers and dry peels (inedible part). Moreover, the inhibitory effect of the onion bulb and peel extracts on rat intestinal α-glucosidase and pancreatic α-amylase of porcine was also evaluated. The antioxidant potential of onion peel and bulb extracts were evaluated using 2,2-diphenyl- 1-picryl hydrazyl (DPPH), ferric-reducing antioxidant power assay (FRAP), 2,2’-azino-bis- 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay, H2O2 radical scavenging activity and Fe2+ chelating activity. Total flavonoids and phenolic content of ethanolic extract of onion peel were significantly greater as compared to that of onion bulb. Ethanolic extract of onion peel also presented better antioxidant and free-radical scavenging activity as compared to the ethanolic extract of bulb, while the aqueous extract of bulb presented weakest antioxidative potential. Onion peel extract's α-glucosidase inhibition potential was also correlated with their phenolic and flavonoid contents. The current findings presented onion peel as a possible source of antioxidative agents and phenolic compounds that might be beneficial against development of various common chronic diseases that might have an association with oxidative stress. Besides, outer dry layers and fleshy peels of onion exhibited higher phenolic content and antioxidant activities, compared [...].


Allium cepa pertence à família Liliaceae e é rica em nutrientes e antioxidantes. Apesar das expressivas aplicações alimentares do bulbo da cebola, sua casca e outras camadas externas são geralmente consideradas resíduos, e seu potencial nutricional e terapêutico ainda é pouco explorado. O presente estudo foi delineado com o objetivo de investigar comparativamente o potencial antioxidante de duas partes de Allium cepa, por exemplo o bulbo (parte comestível) e camadas externas e cascas secas (parte não comestível). Além disso, o efeito inibitório dos extratos do bulbo de cebola e casca sobre a α-glucosidase intestinal de ratos e α-amilase pancreática suína também foi avaliado. O potencial antioxidante dos extratos da casca de cebola e bulbo foi avaliado utilizando-se 2,2-difenil-1-picrilhidrazil (DPPH), método de poder antioxidante de redução do ferro (FRAP), método 2,2’-azino-bis-3-etilbenzotiazolina-6-ácido sulfônico (ABTS) de eliminação de radicais, atividade de eliminação de radicais H2O2 e atividade quelante do Fe2+. Os flavonoides totais e os teores fenólicos do extrato de etanol da casca de cebola foram significativamente maiores quando comparados ao do bulbo. O extrato de etanol da casca de cebola também apresentou melhor atividade antioxidante e eliminação de radicais livres quando comparado ao extrato de etanol do bulbo, enquanto o extrato aquoso de bulbo apresentou menor potencial antioxidante. O potencial de inibição da α-glicosidase dos extratos de casca de cebola correlacionou-se com seus teores fenólicos e de flavonoides. Os resultados encontrados identificaram que a casca de cebola é uma possível fonte de agentes antioxidantes e compostos fenólicos que podem ser benéficos contra o desenvolvimento de várias doenças crônicas que estão associadas ao estresse oxidativo. Além disso, as camadas externas secas e as cascas da cebola exibiram maior conteúdo fenólico e atividades [...].


Subject(s)
Antioxidants/analysis , Onions , Oxidative Stress/drug effects , Glycoside Hydrolase Inhibitors/analysis
7.
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)
Humans , Animals , Tea/chemistry , Catechin/toxicity , Oxidative Stress/drug effects , Genotoxicity , Antioxidants/toxicity , DNA Damage/drug effects , Reactive Oxygen Species , Apoptosis/drug effects
8.
Int. j. morphol ; 40(3): 697-705, jun. 2022. ilus, tab
Article in English | 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
9.
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
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. morphol ; 40(1): 204-209, feb. 2022. ilus
Article in English | LILACS | ID: biblio-1385562

ABSTRACT

SUMMARY: This study aimed to evaluate the effects of six weeks of HIIT on tissue and oxidative damage markers in rats supplemented with Coutoubea spicata fraction. Thirty-two male Wistar rats were divided into 4 groups: Baseline (GB); supplemented with 100 mg/kg of Coutoubea spicata fraction (GSCS); exercised for 6 weeks with the HIIT protocol (GH); supplemented with 100 mg/kg of Coutoubea spicata fraction + HIIT for 6 weeks (GHCS). Exercised animals performed the HIIT protocol (2 x 2). Tissue damage CK, LDH, ALT and AST markers in plasma were analyzed, as well as oxidative stress MDA and SH biomarkers in plasma and in cardiac, hepatic and muscle tissues. The results showed that CK, LDH, AST and ALT enzymes showed increase in GH when compared to GB (p<0.0001). However, CK, AST and ALT markers reduced their concentrations in GHCS when compared to GH (p<0.0001), indicating that Coutoubea spicata supplementation attenuated the damage in muscle and liver tissues induced by HIIT. Plasma, liver and muscle MDA showed increase in GH after HIIT sessions; however, when compared to GHCS, it showed reduced levels (p<0.0001). SH was elevated in the GH group when compared to GB in plasma and liver tissues (p<0.0001); in contrast, reduction in GHCS when compared to GH was observed in plasma, liver and cardiac tissues, demonstrating the redox effect of HIIT on some tissues. Thus, our findings showed that Coutoubea spicata has antioxidant activity, reducing oxidative damage markers and consequently tissue damage in healthy Wistar rats after HIIT protocol, but it also demonstrated redox balance after analyzing oxidative stress markers.


RESUMEN: Este estudio tuvo como objetivo evaluar los efectos de HIIT en los marcadores de daño tisular y oxidativo en ratas suplementadas con Coutoubea spicata durante seis semanas. Treinta y dos ratas Wistar macho se dividieron en 4 grupos: línea de base (GB); suplementados con 100 mg/kg de fracción de Coutoubea spicata (GSCS); ejercitados durante 6 semanas con el protocolo HIIT (GH); suplementado con 100 mg/kg de fracción de Coutoubea spicata + HIIT durante 6 semanas (GHCS). Los animales ejercitados realizaron el protocolo HIIT (2x2). Se analizaron los marcadores de daño tisular CK, LDH, ALT y AST en plasma, así como los biomarcadores de estrés oxidativo MDA y SH en plasma y en tejidos cardiaco, hepático y muscular. Los resultados indicaron que las enzimas CK, LDH, AST y ALT mostraron aumento en GH en comparación con GB (p<0,0001). Sin embargo, los marcadores CK, AST y ALT redujeron sus concentraciones en GHCS en comparación con GH (p<0,0001), lo que indica que la suplementación con Coutoubea spicata atenuó el daño en los tejidos musculares y hepáticos inducido por HIIT. La MDA de plasma, hígado y músculo mostró un aumento en la GH después de las sesiones de HIIT; sin embargo, en comparación con GHCS, mostró niveles reducidos (p<0,0001). Se observó SH elevado en el grupo de GH en comparación con GB en plasma y tejidos hepáticos (p<0,0001); en contraste, se observó una reducción en GHCS en comparación con GH en plasma, hígado y tejidos cardíacos, lo que demuestra el efecto redox de HIIT en algunos tejidos. Por lo tanto, nuestros hallazgos mostraron que Coutoubea spicata tiene actividad antioxidante, con reducción de los marcadores de daño oxidativo y, en consecuencia, el daño tisular en ratas Wistar sanas después del protocolo HIIT, pero además demostró el equilibrio redox después de analizar los marcadores de estrés oxidativo.


Subject(s)
Animals , Male , Rats , Plant Extracts/administration & dosage , Oxidative Stress/drug effects , Gentianaceae/chemistry , High-Intensity Interval Training , Biomarkers , Rats, Wistar
12.
Int. j. morphol ; 40(1): 10-17, feb. 2022. ilus
Article in English | LILACS | ID: biblio-1385564

ABSTRACT

SUMMARY: Reactive Oxygen Species (ROS) are part of the functional balance of various systems, they can generate cellular damage by oxidative stress associated with disease processes such as atherosclerosis, cardiovascular disease, diabetes, and aging. Some studies report that copper induces damage to the endothelium, which could be associated with cardiovascular pathologies. This study was an experimental comparative, prospective, longitudinal, and controlled clinical trial in a murine animal model. Twenty-four male Wistar rats were included, the distribution of the groups was time-depending chronic exposition to copper, and a control group. Results show gradual alterations in the groups treated with copper: areas with loss of the endothelium, signs of disorganization of smooth muscle fibers in the tunica media, as well as areas with the fragmentation of the elastic sheets. A significant statistical difference was observed in the active- Caspase-3 analysis expression in the aortic endothelium and endothelium of the capillaries and arterioles of the lung between the control group vs 300 ppm of copper. Expression of eNOS was detected in the endothelium of the aorta and vessels of the lung. Our study shows histological changes in the walls of the great vessels of intoxicated rats with copper, and the increment of inflammatory cells in the alveoli of the study model, mainly at a high dose of copper exposition. These results will be useful to understand more about the mediators involved in the effect of copper over endothelium and cardiovascular diseases in chronic intoxication in humans.


RESUMEN: Las Especies Reactivas de Oxígeno (ROS) son parte del equilibrio funcional de varios sistemas, pueden generar daño celular por estrés oxidativo asociado a procesos patológicos como aterosclerosis, enfermedades cardiovasculares, diabetes y envejecimiento. Algunos estudios informan que el cobre induce daños en el endotelio, lo que podría estar asociado a patologías cardiovasculares. Este estudio fue un ensayo clínico experimental comparativo, prospectivo, longitudinal y controlado en un modelo animal murino. Se incluyeron veinticuatro ratas Wistar macho, la distribución de los grupos fue la exposición crónica al cobre en función del tiempo y un grupo de control. Los resultados muestran alteraciones graduales en los grupos tratados con cobre: áreas con pérdida del endotelio, signos de desorganización de las fibras musculares lisas en la túnica media, así como áreas con la fragmentación de las láminas elásticas. Se observó una diferencia estadística significativa en la expresión del análisis de caspasa-3 activa en el endotelio aórtico y el endotelio de los capilares y arteriolas del pulmón entre el grupo de control frente a 300 ppm de cobre. Se detectó expresión de eNOS en el endotelio de la aorta y los vasos del pulmón. Nuestro estudio muestra cambios histológicos en las paredes de los grandes vasos de ratas intoxicadas con cobre, y el incremento de células inflamatorias en los alvéolos del modelo de estudio, principalmente a una alta dosis de exposición de cobre. Estos resultados serán útiles para comprender más sobre los mediadores involucrados en el efecto del cobre sobre el endotelio y las enfermedades cardiovasculares en la intoxicación crónica en humanos.


Subject(s)
Animals , Rats , Copper/toxicity , Endothelium/drug effects , Cell Death/drug effects , Rats, Wistar , Oxidative Stress/drug effects , Disease Models, Animal , Nitric Oxide Synthase Type III/metabolism
13.
Int. j. morphol ; 40(1): 157-167, feb. 2022. ilus, tab
Article in English | LILACS | ID: biblio-1385584

ABSTRACT

SUMMARY: Carbon tetrachloride (CCl4) is a manufactured chemical and does not occur naturally in the environment. CCl4 is a clear liquid that evaporates very easily. It has a sweet odor. CCl4 is toxic to the mammalian liver and is hepatocarcinogenic in both rats and mice. Rosemary (Rosmarinus Officinalis) is commonly used as a spice and flavoring agent in food processing. It is known for its antioxidant properties. The present study aims to investigate the antioxidant activity of rosmarinic acid (RA) on CCl4-induced liver toxicity in adult male albino rats. Forty adult male albino rats were divided into 4 groups with 10 rats in each group. Group I (control group). Group II animals received RA at a dose of 50 mg/kg/day by oral gavage for 4 weeks. Group III animals received CCl4 intraperitoneally at a dose of 3ml/kg twice weekly for 4 weeks. Group IV animals received CCl4 Plus RA. At the end of the experiment, liver specimens are processed for histological, immunohistochemical, EM and biochemical studies. Administration of RA deceased the elevated serum liver enzymes (AST, ALT, and ALP), elevated MDA level and immunoexpression of the proapoptotic protein (Bax) induced by CCl4. It increased reduced glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and immunoexpression of the antiapoptotic protein (Bcl2). It also improved the histological and ultrastructural changes induced by CCl4. It appears that Rosmarinic acid has protective effects against CCl4-induced hepatotoxicity as indicated by biochemical, histological, immunohistochemical and ultrastructural results.


RESUMEN: El tetracloruro de carbono (CCl4) es un producto químico fabricado y no se encuentra de forma natural en el medio ambiente. CCl4 es un líquido transparente que se evapora fácilmente; tiene un olor dulce. CCl4 es tóxico para el hígado de los mamíferos y es hepatocarcinogénico tanto en ratas como en ratones. El romero (Rosmarinus officinalis) se usa comúnmente como condimento y agente aromatizante en el procesamiento de alimentos. Es conocido por sus propiedades antioxidantes. El presente estudio tuvo como objetivo investigar la actividad antioxidante del ácido rosmarínico (RA) sobre la toxicidad hepática inducida por CCl4 en ratas albinas macho adultas. Se dividieron cuarenta ratas albinas macho adultas en 4 grupos con 10 ratas en cada grupo. Grupo I (grupo control). Los animales del grupo II recibieron AR a una dosis de 50 mg / kg / día por sonda oral durante 4 semanas. Los animales del grupo III recibieron CCl4 por vía intraperitoneal a una dosis de 3 ml / kg dos veces por semana durante 4 semanas. Los animales del grupo IV recibieron CCl4 Plus RA. Al final del experimento, las muestras de hígado se procesaron para estudios histológicos, inmunohistoquímicos, EM y bioquímicos. La administración de AR eliminó las enzimas hepáticas séricas elevadas (AST, ALT y ALP), el nivel elevado de MDA y la inmunoexpresión de la proteína proapoptótica (Bax) inducida por CCl4. Aumentó el glutatión reducido (GSH), glutatión peroxidasa (GSH-Px), la superóxido dismutasa (SOD) y la inmunoexpresión de la proteína antiapoptótica (Bcl2). También mejoró los cambios histológicos y ultraestructurales inducidos por CCl4. El ácido rosmarínico puede tener efectos protectores contra la hepatotoxicidad inducida por CCl4, tal como lo indican los resultados bioquímicos, histológicos, inmunohistoquímicos y ultraestructurales.


Subject(s)
Animals , Male , Mice , Carbon Tetrachloride/toxicity , Cinnamates/administration & dosage , Depsides/administration & dosage , Chemical and Drug Induced Liver Injury/drug therapy , Antioxidants/administration & dosage , Superoxide Dismutase/analysis , Immunohistochemistry , Cinnamates/pharmacology , Oxidative Stress/drug effects , Microscopy, Electron, Transmission , Depsides/pharmacology , Glutathione Peroxidase/analysis , Malondialdehyde/analysis , Antioxidants/pharmacology
14.
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
15.
Int. j. morphol ; 40(4): 1060-1066, 2022. ilus, tab
Article in English | 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
16.
Int. j. morphol ; 40(4): 874-879, 2022. ilus
Article in English | 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
17.
São Paulo; s.n; s.n; 2022. 74 p. graf.
Thesis in English | LILACS | ID: biblio-1416711

ABSTRACT

Growing evidence indicates that oxidative stress plays an important role in the pathophysiology of many cardiovascular diseases, including atherosclerosis. In this context, the use of bioactive compounds with antioxidant action can bring health benefits, especially in the prevention and control of pathophysiological events. Studies suggest that the polyphenol trans-resveratrol can reduce oxidative stress by acting on the nuclear factor erythroid-2-related factor 2 (Nrf2) and this effect would be associated with dosage. Thus, the present study aimed to investigate the effect of different doses of trans-resveratrol on biomarkers related to atherosclerosis and oxidative stress. In the first step, 27 randomized clinical trials, which evaluated the effect of trans-resveratrol on atherosclerosis-related biomarkers, were classified according to their protocol characteristics and profile of each outcome. Biochemical data from 12 biomarkers were selected to calculate the net change (%). Using multivariate analysis, the trials were distributed into 3 clusters. The studies that composed Clusters II and III were more effective in improving blood pressure and reducing dyslipidemia, respectively. These studies were characterized by a longer intervention time (> 2 months) with doses of around 200-500 mg/day. These results showed that the effects of transresveratrol are mainly related to dosage and intervention time. Based on these results, two doses were selected to apply in an experimental protocol to investigate the effect of trans-resveratrol on hepatic oxidative stress biomarkers mediated by Nrf2 pathway. LDLr(-/-) mice were fed for 8 weeks on a standard diet, followed by over 24 weeks on a Western diet, both containing trans-resveratrol at doses of 250 mg/kg diet/day (low dose resveratrol, LRD) or 400 mg/kg diet/day (high dose resveratrol, HRD). A control group (CONT) was maintained without supplementation. In general, both doses of trans-resveratrol did not affect the body weight and lipid profile of the animals. Only the LRD group showed reduced levels of two important biomarkers of oxidative stress in the liver (GSH/GSSG ratio and malonaldehyde), besides to reduced expression of factor nuclear kappa B (NF-kB). However, contrary to our hypothesis, both doses reduced Nrf2 expression in the liver compared to the CONT group. Regarding inflammatory cytokines, no changes were observed in the levels of TNF-α and IL-10. Furthermore, both doses increased the level of the pro-inflammatory cytokine IL-6. Taken together, our results suggest that trans-resveratrol supplementation at doses lower than 500 mg/day may contribute to the reduction of biomarkers related to atherosclerosis and oxidative stress


Evidências crescentes indicam que o estresse oxidativo desempenha um papel importante na fisiopatologia de muitas doenças cardiovasculares, incluindo a aterosclerose. Nesse contexto, o uso de compostos bioativos com ação antioxidante pode trazer benefícios à saúde, principalmente na prevenção e controle de eventos fisiopatológicos. Estudos sugerem que o polifenol trans-resveratrol pode reduzir o estresse oxidativo atuando na via do fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) e que esse efeito estaria associado a dosagem. Assim, o presente estudo teve como objetivo investigar o efeito de diferentes doses de trans-resveratrol sobre biomarcadores relacionados à aterosclerose e estresse oxidativo. Na primeira etapa, 27 ensaios clínicos randomizados, que avaliaram o efeito do trans-resveratrol em biomarcadores relacionados à aterosclerose, foram classificados de acordo com suas características de protocolo e perfil de cada resultado. Dados bioquímicos de 12 biomarcadores foram selecionados para calcular a variação líquida (%). Usando análise multivariada, os ensaios foram distribuídos em 3 Clusters. Os estudos que compuseram os Clusters II e III foram mais eficazes na melhora da pressão arterial e na redução da dislipidemia, respectivamente. Esses estudos foram caracterizados por um tempo de intervenção mais longo (> 2 meses) com doses de cerca de 200-500 mg/dia. Esses resultados mostraram que os efeitos do transresveratrol estão relacionados principalmente à dosagem e ao tempo de intervenção. Com base nesses resultados, duas doses foram selecionadas para aplicar em um protocolo experimental para investigar o efeito do trans-resveratrol em biomarcadores de estresse oxidativo hepático mediados pela via do Nrf2. Camundongos LDLr(-/-) foram alimentados por 8 semanas com dieta padrão, seguidos por mais de 24 semanas com Western diet, ambos contendo trans-resveratrol nas doses de 250 mg/kg de dieta/dia (baixa dose de resveratrol, LRD) ou 400 mg/kg de dieta/dia (alta dose de resveratrol, HRD). Um grupo controle (CONT) foi mantido sem suplementação. Em geral, ambas as doses de trans-resveratrol não afetaram o peso corporal e o perfil lipídico dos animais. Apenas o grupo LRD apresentou níveis reduzidos de dois importantes biomarcadores de estresse oxidativo no fígado (razão GSH/GSSG e malonaldeído), além da redução da expressão de fator nuclear kappa B (NF-kB). No entanto, ao contrário da nossa hipótese, ambas as doses reduziram a expressão de Nrf2 no fígado em comparação com o grupo CONT. Em relação às citocinas inflamatórias, não foram observadas alterações nos níveis de TNF-α e IL-10. Além disso, ambas as doses aumentaram o nível da citocina pró-inflamatória IL-6. Em conjunto, nossos resultados sugerem que a suplementação de trans-resveratrol em doses menores de 500 mg/dia podem contribuir para a redução de biomarcadores relacionados à aterosclerose e ao estresse oxidativo


Subject(s)
Animals , Male , Female , Mice , Biomarkers/analysis , Randomized Controlled Trials as Topic , Oxidative Stress/drug effects , Atherosclerosis/pathology , Resveratrol/adverse effects , Cardiovascular Diseases/prevention & control , NF-kappa B , Antioxidants/administration & dosage
18.
Arq. bras. cardiol ; 118(2): 435-445, 2022. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1364333

ABSTRACT

Resumo Fundamento O pterostilbeno (PS), um composto polifenólico natural e antioxidante, surge como uma intervenção promissora para minimizar danos do infarto agudo do miocárdio (IAM). Objetivo Este estudo teve como objetivo avaliar o desempenho do PS na promoção da homeostase redox nos pulmões e no ventrículo direito (VD) de animais infartados. Métodos Ratos Wistar machos (60 dias de idade) foram randomizados em três grupos: SHAM, IAM (infarto) e IAM+PS (IAM + pterostilbeno). Sete dias após o procedimento de IAM, os ratos foram tratados com PS (100 mg/kg/dia) por gavagem por oito dias. Os animais foram depois sacrificados e os pulmões e VD foram coletados para análise do balanço redox (diferenças foram consideradas significativas quando p<0,05). Resultados Nossos resultados mostram que o IAM desencadeia a interrupção redox no VD e nos pulmões, o que pode contribuir para danos induzido pelo IAM nesses órgãos. Consistentemente, o PS mitigou o estresse oxidativo e restaurou as defesas antioxidantes (Glutationa - GSH nos pulmões: SHAM = 0,79 ± 0,07; IAM = 0,67 ± 0,05; IAM + PS = 0,86 ± 0,14; p<0,05), indicando seu papel protetor neste cenário. Conclusão Nosso trabalho evidencia o potencial do uso de PS como abordagem terapêutica adjuvante após IAM para proteção dos tecidos pulmonares e cardíacos direitos.


Abstract Background Pterostilbene (PS), a natural and antioxidant polyphenolic compound emerges as a promising intervention in improving the myocardial infarction (MI) damages. Objetives This study aimed to evaluate PS actions in promoting redox homeostasis in lungs and right ventricle (RV) of infarcted animals. Methods Male Wistar rats (60 day-old) were randomized into three groups: SHAM, MI (infarcted), and MI+PS (MI+pterostilbene). Seven days after MI procedure, rats were treated with PS (100 mg/kg/day) via gavage for eight days. Animals were euthanized and the lungs and RV were harvested for analyses of redox balance (Differences were considered significant when p<0.05). Results Our results show that MI triggers a redox disruption scenario in RV and lungs, which can contribute to MI-induced damage on these organs. Consistently, PS mitigated oxidative stress and restored antioxidant defenses (GSH in lungs: SHAM= 0.79±0.07; MI=0.67±0.05; MI+PS=0.86±0.14; p<0.05), indicating its protective role in this scenario. Conclusions Our work evidences the PS potential use as an adjuvant therapeutic approach after MI focusing on protecting pulmonary and right-sided heart tissues.


Subject(s)
Animals , Male , Rats , Stilbenes/pharmacology , Oxidative Stress/drug effects , Heart Ventricles/drug effects , Lung/drug effects , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Rats, Wistar
19.
Braz. arch. biol. technol ; 65: e22200702, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364476

ABSTRACT

Abstract: Boron is one of the most important micronutrients for plants. Plants may suffer from deficiency or with boron toxicity. Boron plays a role in significant physiological and biochemical events in plants such as synthesis of the cell wall, membrane integrity, antioxidation, transport of photosynthesis products to other organs of the plant. The enzyme activities of ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR) and superoxide dismutase (SOD) in three different safflower cultivars (Balcı, Dinçer and Remzibey) subjected to different boric acid concentrations (0, 5, 10, 15 mM) were measured spectrophotometrically, and the changes in the expression levels of the genes that encode these enzymes were obtained by quantitative RT-qPCR. When both the spectrophotometric measurements and the mRNA values were evaluated together, both the activity and mRNA values of APX and GR enzymes were found to be the highest in the Dinçer cultivar among the varieties treated with 15 mM boric acid, while the lowest values of these enzymes were determined in the Remzibey cultivar. According to the RT-qPCR results, the lowest SOD and CAT values were determined in Remzibey. The Dinçer cultivar was found to have the highest antioxidant capacity (APX, GR) to cope with oxidative stress caused by boric acid application at high concentrations. The sensitive Remzibey cultivar was found to have the lowest antioxidant capacity to cope with such oxidative stress. Balcı was found to be closer to Dinçer than to Remzibey in terms of boron tolerance. As a result, the boron-sensitive cultivar had low antioxidant activity.


Subject(s)
Trace Elements/administration & dosage , Boron/administration & dosage , Crop Production , Carthamus tinctorius/metabolism , Antioxidants/metabolism , Trace Elements/toxicity , Boron/toxicity , Gene Expression/drug effects , Oxidative Stress/drug effects , Carthamus tinctorius/enzymology , Carthamus tinctorius/genetics
20.
Odontoestomatol ; 24(39): 1-14, 2022.
Article in Spanish | LILACS, BNUY-Odon, BNUY | ID: biblio-1370336

ABSTRACT

Numerosos reportes demuestran la presencia de biomarcadores de estrés oxidativo en la saliva de fumadores y hay un creciente interés en correlacionar estos procesos moleculares con la etiología de algunas enfermedades orales, como la periodontitis, una enfermedad inmunoinflamatoria crónica relacionada con un desequilibrio de la homeostasis redox celular. Objetivo: realizar una revisión narrativa sobre la relación entre la disminución de la capacidad antioxidante salival inducida por humo de tabaco, la periodontitis y el potencial uso de farmacología redox para el tratamiento de esta patología. Métodos: se realizó una búsqueda bibliográfica en bases de datos como PUBMED (NLM, NIH, NCBI) y SciELO. Resultados: existe evidencia que relaciona la baja capacidad antioxidante salival con un retraso en el restablecimiento de las condiciones normales en la cavidad oral ante el desarrollo de periodontitis. A su vez, el estado inflamatorio asociado colabora sinérgicamente, provocando un mayor daño tisular con pérdida de tejidos de soporte dentario, fenómeno que podría ser modulado por la acción de farmacología redox. Conclusiones: la intervención con farmacología redox, podría atenuar los biomarcadores de progresión de la enfermedad periodontal, constituyendo una herramienta prometedora para utilizar en conjunto con las estrategias de tratamiento tradicionales.


Numerous reports demonstrate the presence of oxidative stress biomarkers in the saliva of smokers and there is a growing interest in correlating these molecular processes with the etiology of some oral diseases, such as periodontitis, a chronic immunoinlammatory disease related to an imbalance of cellular redox homeostasis. Aims: achieve a narrative review on the relationship between the decrease in salivary antioxidant capacity induced by tobacco smoke, periodontitis, and the potential use of redox pharmacology for the treatment of this pathology. Methods: a bibliographic search was carried out in databases such as PUBMED (NLM, NIH, NCBI) and SciELO. Results: there is evidence that relates the low salivary antioxidant capacity with a delay in the reestablishment of normal conditions in the oral cavity before the development of periodontitis. In turn, the associated inflammatory state collaborates synergistically, causing greater tissue damage with loss of dental support tissues, a phenomenon that could be modulated by the action of redox pharmacology. Conclusions: intervention with redox pharmacology could attenuate the biomarkers of periodontal disease progression, constituting a promising tool to be used in conjunction with traditional treatment strategies.


Muitos artigos demonstram a presença de biomarcadores de estresse oxidativo na saliva de fumantes e há um interesse crescente em correlacionar esses processos moleculares com a etiologia de algumas doenças bucais, como a periodontite, uma doença imunoinlamatória crônica relacionada a um desequilíbrio da redox celular homeostase. Objetivo: realizar uma revisão narrativa sobre a relaçã o entre a diminuiçã o da capacidade antioxidante salivar induzida pela fumaça do tabaco, periodontite e o uso potencial da farmacologia redox para o tratamento desta patologia. Métodos: uma pesquisa bibliográica foi realizada usando bases de dados como PUBMED (NLM, NIH, NCBI) e SciELO. Resultados: há evidências que relacionam a baixa capacidade antioxidante salivar com o retardo no restabelecimento das condições normais da cavidade oral antes do desenvolvimento da periodontite. Por sua vez, o estado inflamatório associado colabora sinergicamente, causando maior dano tecidual com perda de tecidos de suporte dentário, fenômeno que poderia ser modulado pela açã o da farmacologia redox. Conclusões: a intervençã o com a farmacologia redox poderia atenuar os biomarcadores de progressã o da doença periodontal, constituindo-se em uma ferramenta promissora para ser utilizada em conjunto com estratégias tradicionais de tratamento.


Subject(s)
Humans , Periodontitis/etiology , Periodontitis/drug therapy , Saliva/metabolism , Oxidative Stress , Tobacco Smoking/adverse effects , Antioxidants/therapeutic use , Oxidation-Reduction , Biomarkers , Oxidative Stress/drug effects , Homeostasis
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