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1.
Article in English | WPRIM | ID: wpr-939787

ABSTRACT

OBJECTIVE@#To investigate the protective effects of Schisandra chinensis oil (SCEO) against aristolochic acid I (AA I)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.@*METHODS@#C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AA I group, and AA I +SCEO (0.25, 0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AA I groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AA I (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr), as well as renal malondialdehyde (MDA), glutathione, r-glutamyl cysteingl+glycine (GSH), and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. In vitro, SCEO (40 µ g/mL) was added 12 h before treatment with AA I (40 µ mol/mL for 48 h) in human renal proximal tubule cell line (HK-2), then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry.@*RESULTS@#SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AA I-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr (P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA, GSH and SOD (P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 µ g/mL inhibited apoptosis and ROS generation (P<0.05 or P<0.01).@*CONCLUSIONS@#SCEO can alleviate AA I-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.


Subject(s)
Animals , Apoptosis , Aristolochic Acids/toxicity , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A2/metabolism , Glutathione/metabolism , Kidney/drug effects , Kidney Diseases/drug therapy , Mice , Mice, Inbred C57BL , Oxidative Stress , Plant Oils/therapeutic use , Protective Agents/therapeutic use , Reactive Oxygen Species/metabolism , Schisandra , Superoxide Dismutase/metabolism
2.
Acta cir. bras ; 37(9): e370904, 2022. ilus, tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1413622

ABSTRACT

Purpose: This study investigated the effects of oral administration of Clostridium butyricum (C. butyricum) on inflammation, oxidative stress, and gut flora in rats with hepatic ischemia reperfusion injury (HIRI). Methods: The rats from C. butyricum group were given C. butyricum for 5 days. Then, hepatic ischemia for 30 min and reperfusion for 6 h were performed in all the rats. After the animals were sacrificed, alanine transaminase (ALT), aspartate aminotransferase (AST), lipopolysaccharide (LPS) in serum, short-chain fatty acids (SCFAs), and gut microbiota composition in feces, and malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), Toll-like receptor 4 (TLR4), nuclear factor-kappa Bp65 (NF-κBp65) and histological analysis in the liver were performed. Results: The rats given C. butyricum showed decreased ALT, AST, LPS, and MDA; improved GSH and histological damage; changes in SCFAs; declined TNF-α, IL-6, TLR4, and pNF-κBp65/NF-κBp65; and changes in the gut microbial composition, which decreased the Firmicutes/Bacteroidetes ratio and increased the relative abundance (RA) of probiotics. Conclusions: C. butyricum supplementation protected against HIRI by regulating gut microbial composition, which contributed to the decreased LPS and attenuation of inflammation and oxidative stress. These indicate C. butyricum may be a potent clinical preoperative dietary supplement for HIRI.


Subject(s)
Animals , Rats , Reperfusion Injury/veterinary , Protective Agents/administration & dosage , Clostridium butyricum , Fatty Acids, Volatile , Oxidative Stress , Liver Diseases/therapy
3.
Acta cir. bras ; 37(2): e370204, 2022. graf
Article in English | LILACS, VETINDEX | ID: biblio-1374066

ABSTRACT

Purpose: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. Methods: PCCL was orally administered at a dose of 20 mg·kg­1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg­1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1ß levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. Results: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. Conclusions: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.


Subject(s)
Animals , Mice , Polysaccharides/therapeutic use , Cuscuta/chemistry , Mucositis/drug therapy , Fluorouracil/adverse effects , Protective Agents/analysis
4.
Article in English | WPRIM | ID: wpr-878319

ABSTRACT

Objective@#Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM @*Methods@#EVs were isolated from the serum of healthy subjects, quantified @*Results@#PM @*Conclusions@#EVs treatment promotes cell survival and attenuates PM


Subject(s)
A549 Cells , Air Pollutants/toxicity , Apoptosis/drug effects , Cell Survival/drug effects , Extracellular Vesicles , Humans , Male , Middle Aged , Particulate Matter/toxicity , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Serum
5.
Int. j. morphol ; 38(4): 876-881, Aug. 2020. graf
Article in English | LILACS | ID: biblio-1124869

ABSTRACT

Acetaminophen (also called paracetamol, or APAP) causes acute kidney injury after accidental or intentional ingestion of a toxic dose of the drug. We tested whether the antioxidant and anti-inflammatory agent, quercetin (QUR) given alone can protect against acute nephrotoxicity induced by APAP overdose in a rat model of APAP-induced acute kidney injury. Rats were either given a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Kidneys were examined by light microscopy after staining with hematoxylin and eosin (H&E) and collected blood samples were assayed for biomarkers of oxidative stress, inflammation, and kidney injury. H&E stained sections of kidney from the model group of rats (APAP) showed substantial damage to the kidney architecture as demonstrated by widening of Bowman's space, tubular dilatation, vacuolization of tubular epithelium, and congested dilated blood vessels, which were partially protected by QUR. In addition, APAP significantly (p<0.05) increased blood levels of urea, creatinine, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6), which were significantly (p<0.05) reduced by QUR. These results indicate that quercetin partially protects against APAP-induced acute kidney injury in rats, which is associated with the inhibition of biomarkers of oxidative stress and inflammation and kidney injury.


El acetaminofeno (también llamado paracetamol o DCI) causa daño renal agudo después de la ingestión accidental o intencional de una dosis tóxica del medicamento. En el estudio analizamos si el agente antioxidante y antiinflamatorio, la quercetina (QUR) administrada sola, puede proteger contra la nefrotoxicidad aguda inducida por sobredosis de DCI en un modelo de rata. Las ratas recibieron una dosis única de DCI (2 g / kg) antes de ser sacrificadas después de 24 horas o fueron pretratadas durante 7 días con QUR (50 mg / kg) antes de recibir una dosis única de DCI y luego sacrificadas 24 horas post ingestión. Los riñones se examinaron mediante microscopía óptica después de la tinción con hematoxilina y eosina (H&E) y las muestras de sangre recolectadas se analizaron para detectar biomarcadores de estrés oxidativo, inflamación y daño renal. Las secciones de riñón teñidas con H&E del grupo modelo de ratas (DCI) mostraron un daño sustancial a la arquitectura del riñón, como lo demuestra la ampliación del espacio de Bowman, la dilatación tubular, la vacuolización del epitelio tubular y los vasos sanguíneos dilatados congestionados, que estaban parcialmente protegidos por QUR. Además, DCI aumentó significativamente (p <0,05) los niveles sanguíneos de la urea, creatinina, malondialdehído (MDA), factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6), los que fueron reducidos significativamente (p < 0,05) por QUR. Estos resultados indican que la quercetina protege parcialmente contra la lesión renal aguda inducida por DCI en ratas, asociada con la inhibición de biomarcadores de estrés oxidativo, inflamación y lesión renal.


Subject(s)
Animals , Rats , Quercetin/administration & dosage , Acute Kidney Injury/chemically induced , Acetaminophen/toxicity , Antioxidants/administration & dosage , Quercetin/pharmacology , Biomarkers/analysis , Oxidative Stress/drug effects , Protective Agents , Creatinine , Disease Models, Animal , Inflammation , Kidney/drug effects , Antioxidants/pharmacology
6.
Int. j. morphol ; 38(4): 940-946, Aug. 2020. tab, graf
Article in English | LILACS | ID: biblio-1124880

ABSTRACT

Solanum nigrum (SLN), commonly known as African nightshade, is used as a vegetable as well as in the management and treatment of various ailments including gastric ulcers. We analyzed, both grossly and microscopically using H&E, Masson's trichrome and PSA staining methods, the protective effects of aqueous leaf extracts of three Kenyan SLN genotypes namely S. scabrum (SSB), S. sarrachoides (SSR) and S. villosum (SVL) on ethanol-induced gastric lesions in rats. There was evidence of gastro-protection by all the three genotypes with the SSB showing the highest ulcer inhibition score (76.37 %) followed by SSR (72.51 %) and SVL (63.30 %). SLN-pretreated rats showed less areas of gastric mucosal surface erosion. Additionally in the pretreated animals, the depth of the ulcers were markedly reduced, reaching only the gastric pit region except in those treated with SVL where the ulcers penetrated slightly more deeply to affect the gastric glands. Compared with controls, the mean microscopic ulcer index decreased 5.07, 3.55 and 2.37-fold in rats pretreated with SSB, SSR and SVL extracts respectively. Results of this work show extracts of the three SLN genotypes to have antiulcerogenic potential but at varied strengths, thus confirming earlier reports that phytoconstituents and hence the efficacy of a medicinal plant may be influenced by genetic factors.


Solanum nigrum (SLN), comúnmente conocida como la solanácea africana, se usa como vegetal, para el tratamiento de diversas dolencias incluyendo las úlceras gástricas. Analizamos de forma macro y microscópica, de forma macroscópica y microscópica, utilizando para ello tinciones de H&E, tricrómico de Masson y PSA los efectos protectores de extractos acuosos de hojas de tres genotipos SLN de Kenia: S. scabrum (SSB), S. sarrachoides (SSR) and S. villosum (SVL) en lesiones gástricas inducidas por etanol en ratas. Hubo evidencia de gastroprotección por parte de los tres genotipos con el SSB mostrando el puntaje más alto de inhibición de la úlcera (76,37 %) seguido de SSR (72,51 %) y SVL (63,30 %). Las ratas tratadas previamente con SLN mostraron menos áreas de erosión de la superficie de la mucosa gástrica. Además, en los animales pretratados, la profundidad de las úlceras se redujo notablemente, llegando solo a la región del fondo gástrico, excepto en aquellos tratados con SVL donde las úlceras penetraron un poco más profundamente para afectar las glándulas gástricas. En comparación con los controles, el índice medio de úlcera microscópica disminuyó 5,07, 3,55 y 2,37 veces en ratas pretratadas con extractos de SSB, SSR y SVL, respectivamente. Los resultados de este trabajo muestran que los extractos de los tres genotipos de SLN tienen potencial antiulcerogénico en diferentes concentraciones, lo que confirma informes anteriores que los fitoconstituyentes y la eficacia de una planta medicinal pueden estar influenciados por factores genéticos.


Subject(s)
Animals , Rats , Stomach Ulcer/drug therapy , Plant Extracts/therapeutic use , Solanum nigrum/chemistry , Anti-Ulcer Agents/therapeutic use , Stomach/drug effects , Rats, Wistar , Protective Agents , Plant Preparations/pharmacology , Kenya , Anti-Ulcer Agents/pharmacology
7.
Int. j. morphol ; 38(3): 804-810, June 2020. tab, graf
Article in English | LILACS | ID: biblio-1098323

ABSTRACT

Honey is a natural antioxidant that its protective effects have been proven against ischemia-reperfusion (IR) injury. The aim of this study was to evaluate the ameliorative effect of Persian Honey, Apis mellifera meda skorikov, on gastrocnemius muscle IR injury. Eighty adult male Sprague-Dawley rats weighing 250-300 g were used. They were divided into ten groups (N=8 per group). The ischemia was conducted with a silk suture 6-0 using the slipknot technique. All groups were rendered in ischemic for 3 h, and reperfused for various times of 3 days (3-day reperfusion), 7 days (7-day reperfusion), 14 days (14-day reperfusion), and 28 days (28-day reperfusion). Half of the groups had experimental honey (5 %) treatment immediately after ischemia. After reperfusion, the rats, based on the grouping, were killed with high doses of anesthetic, and the gastrocnemius muscles were removed and fixed. After the tissue processing, the evaluation of edema and mast cells infiltration was performed with hematoxylin-eosin and toluidine blue staining, respectively. TNF-α was detected with immunohistochemistry method. The amount of TNF-α as an index of acute inflammatory except the 3rd day significantly decreased on the other day of reperfusion (7th, 147th and 287th days). The mast cells infiltration was significantly decreased on 77th and 147th days. The tissue edema was decreased significantly in honey administrated group in the comparison with placebo groups. Honey administration can reduce damage caused by ischemia-reperfusion in the rat gastrocnemius muscle.


La miel es un antioxidante natural; sus efectos protectores han sido probados contra la lesión por isquemiareperfusión (IR). El objetivo de este estudio fue evaluar el efecto de mejora de la miel persa Apis mellifera meda skorikov, en la lesión por IR del músculo gastrocnemio. Se utilizaron 80 ratas Sprague-Dawley macho adultas con un peso entre 250 y 300 g divididas en diez grupos (N = 8 por grupo). La isquemia se realizó con una sutura de seda 6-0 utilizando la técnica slipknot permaneciendo isquémicos durante 3 h. La reperfusión se realizó durante varios tiempos de 3 días, 7 días (reperfusión de 7 días), 14 días (reperfusión de 14 días) y 28 días (28 días reperfusión). La mitad de los grupos recibió tratamiento experimental con miel (5 %) inmediatamente después de la isquemia. Después de la reperfusión, las ratas, fueron sacrificadas con altas dosis de anestésico, y los músculos gastrocnemios fueron removidos y fijados. Después de procesar el tejido, se realizó la evaluación del edema y la infiltración de mastocitos se realizó con tinción de hematoxilina-eosina y azul de toluidina, respectivamente. TNF-α se detectó con el método de inmunohistoquímica. La cantidad de TNF-α como índice de inflamación inflamatoria aguda, excepto en el tercer día, disminuyó significativamente al día siguiente de la reperfusión (7, 14 y 28 días). La infiltración de mastocitos disminuyó significativamente a los 7 y 14 días. El edema tisular disminuyó significativamente en el grupo administrado con miel en comparación con los grupos placebo. El tratamiento con miel puede reducir el daño causado por la isquemia-reperfusión en el músculo gastrocnemio de la rata.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/complications , Apis mellifica/administration & dosage , Muscle, Skeletal/injuries , Honey , Immunohistochemistry , Reperfusion Injury/drug therapy , Apis mellifica/pharmacology , Rats, Sprague-Dawley , Muscle, Skeletal/drug effects , Protective Agents
8.
Braz. j. otorhinolaryngol. (Impr.) ; 86(1): 30-37, Jan.-Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1089360

ABSTRACT

Abstract Introduction Ototoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea. Objectives The possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy. Methods This study was conducted on 21 Wistar Albino rats in four groups. 1 mL/kg/day three times in total intraperitoneal (i.p.) Saline (n = 5), 500 mg/kg/day i.p. three times in total N-acetylcysteine (n = 5), i.p. 15 mg/kg cisplatin alone (single dose) (n = 5) and i.p. 15 mg/kg cisplatin plus 500 mg/kg/day N-acetylcysteine (n = 6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy. Results Auditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin + N-acetylcysteine group. Conclusion Cisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4 h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.


Resumo Introdução A ototoxicidade é um problema que pode ocorrer após certos tipos de tratamentos para condições graves de saúde. Às vezes é inevitável quando o tratamento da doença é necessário. A cisplatina é um agente antineoplásico cujo uso em pesquisas anteriores demonstrou aumentar os radicais livres de nitrogênio e espécies reativas de oxigênio que danificam as células ciliadas e resultam em ototoxicidade. Por outro lado, a N-acetilcisteína, que já demonstrou diminuir a ototoxicidade causada por diferentes agentes, é conhecida por ser um potente antioxidante in vitro. Provavelmente a N-acetilcisteína, além de seu efeito antioxidante, bloqueia uma cascata onde espécies reativas de oxigênio resultam em apoptose na cóclea. Objetivos Estudar o possível efeito preventivo da N-acetilcisteína na ototoxicidade por cisplatina por meio de potencial evocado auditivo de tronco encefálico, emissões otoacústicas e investigação histopatológica da cóclea por microscopia eletrônica de varredura. Método Este estudo foi realizado em 21 ratos albinos Wistar, separados em quatro grupos. Foram administrados: 1 mL/kg/dia intraperitoneal (i.p.) de solução salina (n = 5), três vezes no total; 500 mg/kg/dia i.p. de N-acetilcisteína (n = 5), três vezes no total; 15 mg/kg i.p. (dose única) somente de cisplatina (n = 5) e 15 mg/kg i.p. de cisplatina e 500 mg/kg/dia i.p. de N-acetilcisteína (n = 6). Os ratos foram anestesiados para estudo dos testes auditivos antes e depois do experimento. Os ratos foram sacrificados para investigação da cóclea por microscopia eletrônica de varredura. Resultados Os potenciais evocados auditivos de tronco encefálico e os valores das emissões otoacústicas estavam atenuados no grupo cisplatina. O grupo que recebeu N-acetilcisteína além da cisplatina apresentou melhores limiares de respostas auditivas do tronco encefálico e emissões otoacústicas. As amostras obtidas do grupo cisplatina apresentaram irregularidades de superfície, áreas de degeneração, com perdas graves totais ou parciais de estereocílios. As alterações foram mais leves no grupo cisplatina + N-acetilcisteína. Conclusão A ototoxicidade por cisplatina pode ser detectada por meio de potenciais evocados auditivos de tronco encefálico e pelo teste de emissões otoacústicas em ratos. A N-acetilcisteína pode proteger as células cocleares contra alterações histopatológicas. Concluímos que a N-acetilcisteína administrada 4 horas após a injeção de cisplatina tem potencial efeito otoprotetor contra a ototoxicidade por cisplatina e pode ser utilizada em ensaios clínicos.


Subject(s)
Animals , Male , Acetylcysteine/administration & dosage , Cisplatin/adverse effects , Protective Agents/administration & dosage , Ototoxicity/etiology , Antineoplastic Agents/adverse effects , Antioxidants/administration & dosage , Acetylcysteine/pharmacology , Microscopy, Electron, Scanning , Evoked Potentials, Auditory, Brain Stem , Rats, Wistar , Cochlea/pathology , Apoptosis , Hair Cells, Auditory, Outer/drug effects , Hair Cells, Auditory, Outer/pathology , Protective Agents/pharmacology , Disease Models, Animal , Stereocilia/drug effects , Stereocilia/pathology , Ototoxicity/prevention & control , Hearing Tests , Antioxidants/pharmacology
9.
Braz. j. med. biol. res ; 53(9): e9375, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132551

ABSTRACT

In this paper, we complement our previous study on the antiproliferative activity of Calea fruticosa (Asteraceae) by isolating the compounds apigenin-4',7-dimethyl ether (1), budlein A (2), quercetin (3), and cichoriin (4) from the plant's aerial parts. The antiproliferative activity of these compounds was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method against human tumor cell lines. Compound 3 displayed moderate antiproliferative activity in three cell lines (HCT-116, PC-3, and SF-295, with cell growth inhibition values of 72.97, 74.55, and 68.94%) and high antiproliferative activity (90.86%) in the HL-60 cell line. The in vitro sun protection factor (SPF) of the extracts and compound 4, with and without sunscreen, was determined by a spectrophotometric method. The ethanol extract exhibited the highest SPF (9.67) at a concentration of 0.100 mg/mL, while compound 4, isolated from this extract, showed a SPF of 13.79 at the same concentration. A relative increased efficacy of SPF was observed for the extracts and compound 4 when sunscreen was also used. Compound 4 has not been reported previously from any species within the genus Calea. Compounds 1-4 were obtained from this species for the first time.


Subject(s)
Humans , Plant Extracts , Asteraceae , Protective Agents , Cell Line, Tumor , Cell Proliferation/drug effects
10.
Braz. j. med. biol. res ; 53(7): e9271, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132527

ABSTRACT

Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.


Subject(s)
Quinolines/therapeutic use , Asthma/drug therapy , Anti-Asthmatic Agents/therapeutic use , Protective Agents/therapeutic use , Cough/drug therapy , RNA, Long Noncoding/metabolism , Acetates/therapeutic use , Asthma/blood , Cough/blood , Disease Models, Animal , Mice, Inbred BALB C
11.
Braz. j. med. biol. res ; 53(10): e9183, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132479

ABSTRACT

H1N1 virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. There is currently no effective strategy against virus infection in lung. The present study evaluated the protective roles of a natural compound, lapiferin, in H1N1 virus-induced pulmonary inflammation in mice and in cultured human bronchial epithelial cells. Initially, Balb/C mice were grouped as Control, H1N1 infection (intranasally infected with 500 plaque-forming units of H1N1 virus), lapiferin (10 mg/kg), and H1N1+lapiferin (n=10/group). Lung histology, expression of inflammatory factors, and survival rates were assessed after 14 days of exposure. Administration of lapiferin significantly alleviated the virus-induced inflammatory infiltrate in lung tissues. Major pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were decreased at both mRNA and protein levels by lapiferin administration in the lung homogenate. Lapiferin also reduced inflammatory cell numbers in bronchoalveolar fluid. Mechanistically, lapiferin suppressed the transcriptional activity and protein expression of NF-κB p65, causing inhibition on NF-κB signaling. Pre-incubation of human bronchial epithelial cells with an NF-κB signaling specific activator, ceruletide, significantly blunted lapiferin-mediated inhibition of pro-inflammatory cytokines secretion in an air-liquid-interface cell culture experiment. Activation of NF-κB signaling also blunted lapiferin-ameliorated inflammatory infiltrate in lungs. These results suggested that lapiferin was a potent natural compound that served as a therapeutic agent for virus infection in the lung.


Subject(s)
Humans , Animals , Rabbits , Pneumonia , Sesquiterpenes/pharmacology , NF-kappa B/metabolism , Protective Agents/pharmacology , Influenza A Virus, H1N1 Subtype , Signal Transduction , Cytokines , Inflammation
12.
Article in English | WPRIM | ID: wpr-829020

ABSTRACT

Objective@#This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B (AFB ) in rats.@*Methods@#Forty Sprague Dawley rats were randomly divided into control, AFB , AFB + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB and AFB + PCB2 groups were intraperitoneally injected with AFB (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured.@*Results@#AFB significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB .@*Conclusion@#Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB .


Subject(s)
Aflatoxin B1 , Toxicity , Animals , Biflavonoids , Pharmacology , Catechin , Pharmacology , Chemical and Drug Induced Liver Injury , Drug Therapy , Male , Poisons , Toxicity , Proanthocyanidins , Pharmacology , Protective Agents , Pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley
13.
Article in Chinese | WPRIM | ID: wpr-828388

ABSTRACT

Schisandra is the mature fruit of Schisandra chinensis(known as "north Schisandra") or S. shenanthera(known as "south Schisandra"). S. chinensis contains a variety of lignans, volatile oils, polysaccharides, organic acids and other chemical constituents; among them, lignans are recognized as the characteristic active components. Clinical studies have found that Schisandra and Schisandra-related products have a better effect in the prevention and treatment of viral hepatitis, drug-induced liver injury, liver cirrhosis, liver failure and other liver diseases. Modern pharmacological studies have demonstrated that Schisandra has a variety of pharmacological activities, such as anti-inflammation, antioxidation, anticancer, regulation of nuclear receptor, antivirus, regulation of cytochrome P450 enzyme, inhibition of liver cell apoptosis and promotion of liver regeneration. This paper reviews the studies about the applications and mechanism of Schisandra in the prevention and treatment of liver diseases, in the expectation of providing guidance for the development of hepatoprotective drugs from Schisandra and the clinical applications of Schisandra-related products.


Subject(s)
Chemical and Drug Induced Liver Injury , Drugs, Chinese Herbal , Fruit , Chemistry , Humans , Lignans , Protective Agents , Schisandra
14.
Article in English | WPRIM | ID: wpr-827262

ABSTRACT

BACKGROUND@#Pilea umbrosa (Urticaceae) is used by local communities (district Abbotabad) for liver disorders, as anticancer, in rheumatism and in skin disorders.@*METHODS@#Methanol extract of P. umbrosa (PUM) was investigated for the presence of polyphenolic constituents by HPLC-DAD analysis. PUM (150 mg/kg and 300 mg/kg) was administered on alternate days for eight weeks in rats exposed with carbon tetrachloride (CCl). Serum analysis was performed for liver function tests while in liver tissues level of antioxidant enzymes and biochemical markers were also studied. In addition, semi quantitative estimation of antioxidant genes, endoplasmic reticulum (ER) induced stress markers, pro-inflammatory cytokines and fibrosis related genes were carried out on liver tissues by RT-PCR analysis. Liver tissues were also studied for histopathological injuries.@*RESULTS@#Level of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and glutathione (GSH) decreased (p < 0.05) whereas level of thiobarbituric acid reactive substance (TBARS), HO and nitrite increased in liver tissues of CCl treated rat. Likewise increase in the level of serum markers; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total bilirubin was observed. Moreover, CCl caused many fold increase in expression of ER stress markers; glucose regulated protein (GRP-78), x-box binding protein1-total (XBP-1 t), x-box binding protein1-unspliced (XBP-1 u) and x-box binding protein1-spliced (XBP-1 s). The level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) was aggregated whereas suppressed the level of antioxidant enzymes; γ-glutamylcysteine ligase (GCLC), protein disulfide isomerase (PDI) and nuclear erythroid 2 p45-related factor 2 (Nrf-2). Additionally, level of fibrosis markers; transforming growth factor-β (TGF-β), Smad-3 and collagen type 1 (Col1-α) increased with CCl induced liver toxicity. Histopathological scrutiny depicted damaged liver cells, neutrophils infiltration and dilated sinusoids in CCl intoxicated rats. PUM was enriched with rutin, catechin, caffeic acid and apigenin as evidenced by HPLC analysis. Simultaneous administration of PUM and CCl in rats retrieved the normal expression of these markers and prevented hepatic injuries.@*CONCLUSION@#Collectively these results suggest that PUM constituted of strong antioxidant chemicals and could be a potential therapeutic agent for stress related liver disorders.


Subject(s)
Animals , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Drug Therapy , Pathology , Endoplasmic Reticulum Stress , Fibrosis , Drug Therapy , Genetics , Inflammation , Drug Therapy , Genetics , Liver , Metabolism , Male , Protective Agents , Pharmacology , Rats , Rats, Sprague-Dawley , Urticaceae , Chemistry
15.
Rev. Esc. Enferm. USP ; 54: e03618, 2020. tab, graf
Article in English, Portuguese | LILACS, BDENF | ID: biblio-1136623

ABSTRACT

RESUMO Objetivo Desenvolver protetor nasal anatômico para recém-nascidos em uso de pronga. Método Estudo descritivo e de produção tecnológica baseado no Processo de Desenvolvimento de Produto, que envolveu as fases de projeto informacional, projeto conceitual e projeto detalhado, entre março de 2017 e fevereiro de 2019. Resultados Alcançou-se o desenho e materialização dos protetores nasais em placas de hidrocoloide. Estes foram reprocessados por cinco métodos de esterilização: radiação ultravioleta e gama, formaldeído gasoso, plasma de peróxido de hidrogênio e vapor saturado sob pressão. Os testes microbiológicos indicaram crescimento bacteriano após processamento por formaldeído e radiação ultravioleta. A radiação gama garantiu a esterilidade e estabilidade do material. Conclusão Após os testes, foram alcançadas três classificações de protetores nasais de hidrocoloide com características seguras e promissoras para a continuação de estudos, visando à avaliação clínica em recém-nascidos em uso de pronga.


RESUMEN Objetivo Desarrollar un protector nasal anatómico para los recién nacidos usando prongs. Método Estudio descriptivo y tecnológico de producción basado en el Proceso de Desarrollo de Productos, que incluyó las fases de diseño informativo, diseño conceptual y diseño detallado, entre marzo de 2017 y febrero de 2019. Resultados Se logró el diseño y la materialización de protectores nasales en placas hidrocoloides. Estos fueron reprocesados por cinco métodos de esterilización: radiación ultravioleta y gamma, formaldehído gaseoso, plasma de peróxido de hidrógeno y vapor saturado a presión. Las pruebas microbiológicas indicaron un crecimiento bacteriano después del procesamiento por medio de formaldehído y radiación ultravioleta. La radiación gamma aseguró la esterilidad y la estabilidad del material. Conclusión Después de las pruebas, se lograron tres clasificaciones de protectores nasales hidrocoloides con características seguras y prometedoras para la continuación de los estudios, con el objetivo de la evaluación clínica en los recién nacidos utilizando prongs.


ABSTRACT Objective To develop an anatomical nasal protector for newborns using prongs. Method A descriptive study and technological production based on the Product Development Process, which involved informational design, conceptual design and detailed design phases, between March 2017 and February 2019. Results The design and materialization of nasal protectors were achieved in hydrocolloid plates. These were reprocessed by five sterilization methods: ultraviolet and gamma radiation, gaseous formaldehyde, hydrogen peroxide plasma and saturated steam under pressure. Microbiological tests indicated bacterial growth after processing by formaldehyde and ultraviolet radiation. Gamma radiation guaranteed the sterility and stability of the material. Conclusion Three classifications of nasal hydrocolloid protectors were achieved after the tests, with safe and promising characteristics to continue studies aiming at the clinical evaluation in newborns using prongs.


Subject(s)
Wounds and Injuries , Infant, Newborn , Nose , Technology , Protective Agents
16.
Acta cir. bras ; 35(1): e202000104, 2020. graf
Article in English | LILACS | ID: biblio-1088525

ABSTRACT

Abstract Purpose Glutamine, as an essential part of enteral nutrition and parenteral nutrition agent, has been widely recognized to be a kind of important intestinal mucosa protectant in clinical practice and experimental research. However, the mechanisms of its protective effects are still not fully understand. Consequently, this study aimed to explore the potential mechanism of glutamine on ischemia-reperfusion (I/R) injury induced endoplasmic reticulum (ER) stress in intestine. Methods An experimental model of intestinal I/R in rats was established by 1 hour occlusion of the superior mesenteric artery followed by 3 hours of reperfusion. Morphologic changes of intestinal mucosa, apoptosis of epithelial cells, and expression of intestinal Grp78, Gadd153, Caspase-12, ATF4, PERK phosphorylation (P-PERK) and elF2αphosphorylation(P-elF2α) were determined. Results After I/R, the apoptotic index of intestinal mucosa epithelial cells observably increased with notable necrosis of intestinal mucosa, and the expressions of Grp78, Gadd153, Caspase-12, ATF4, P-PERK and P-elF2αall were increased. However, treatment with glutamine could significantly relieve intestinal I/R injury and apoptosis index. Moreover, glutamine could clearly up-regulate the expression of Grp78, restrain P-PERK and P-elF2α, and reduce ATF4, Gadd153 and Caspase-12 expressions. Conclusion Glutamine may be involved in alleviating ER stress induced intestinal mucosa cells apoptosis.


Subject(s)
Animals , Male , Reperfusion Injury/prevention & control , Apoptosis/drug effects , Protective Agents/pharmacology , Endoplasmic Reticulum Stress/drug effects , Glutamine/pharmacology , Intestinal Mucosa/drug effects , RNA, Messenger/drug effects , Rats, Sprague-Dawley , Mesenteric Artery, Superior/injuries , eIF-2 Kinase/drug effects , Models, Animal , Activating Transcription Factor 4/drug effects , Transcription Factor CHOP/drug effects , Caspase 12/drug effects , Heat-Shock Proteins/drug effects , Intestinal Mucosa , Intestinal Mucosa/ultrastructure
17.
Acta cir. bras ; 35(4): e202000401, 2020. tab, graf
Article in English | LILACS | ID: biblio-1130631

ABSTRACT

Abstract Purpose To evaluate the effect of N-Acetylcysteine (NAC) in newborn rats submitted to hypoxia and reoxygenation (H/R) conditions in an experimental model of necrotizing enterocolitis. Methods Eight pregnant rats and their 70 cubs were used (5 groups) and exposed to H/R conditions and received NAC at different times. The animals in the H/R groups were placed in a gas chamber (100% CO2) for 10 minutes and then reoxygenated for 10 minutes (100% O2), twice a day for the first three days of life, with a six-hour span between events. On the third day of life, the animals were anesthetized, laparotomized and the intestines were resected. Results The H/R and NAC groups showed changes in the intestinal wall in relation to the number, height and width of the villi when compared to the control group (p<0.0001), but with better preservation of structures in the NAC group. There were no differences between groups regarding the number (%) of mitoses. Conclusion The administration of NAC decreased the lesions in the intestinal wall of rats submitted to H/R, therefore suggesting that this drug can be used to prevent the development of necrotizing enterocolitis in newborns.


Subject(s)
Animals , Male , Female , Pregnancy , Acetylcysteine/pharmacology , Protective Agents/pharmacology , Enterocolitis, Necrotizing/prevention & control , Ileum/drug effects , Ileum/pathology , Hypoxia/pathology , Reference Values , Time Factors , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Disease Models, Animal
18.
Braz. arch. biol. technol ; 63: e20190311, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132265

ABSTRACT

Abstract Nonsteroidal anti-inflammatory drugs (NSAID) are among the aggressive factors causing gastric ulcer. They cause oxidative damage in the gastric tissue and lead to intracellular calcium deposition. Lercanidipine is a calcium channel blocker derived from the third generation dihydropyridine. The aim of this study is to analyse the effect of lercanidipine on indomethacin-induced gastric ulcers. A total of 24 albino Wistar male rats were divided into four groups; those who received indomethacin 25 mg/kg (IND), 5 mg mg/kg lercanidipine +25 mg/kg indomethacin (LC-5), 10 mg/kg lercanidipine+25mg/kg indomethacin (LC-10) and healthy rats who received 0.5 mL distilled water. Six hours after the application of indomethacin, the animals were sacrificed by high dose thiopental sodium. The stomachs of the animals were excised to perform a macroscopic analysis and the ulcerous region was measured on millimeter paper. All the stomachs were subjected to a biochemical analysis. Macroscopic analysis revealed hyperaemia on the gastric surface of the indomethacin group. Ulcerous tissues formed by oval, circular or irregular mucosal defects in varying diameters and depths were observed on the whole surface of the stomach. Hyperaemia was lower and ulcerous region was smaller in groups LC-5 and LC-10 compared to IND group. Malondialdehyde and myeloperoxidase levels were significantly lower and total glutathione and cyclooxygenase-1 activity were higher in groups LC-5 and LC-10. Lercanidipine did not change the cyclooxygenase-2 activity. Lercanidipine in doses 10 mg/kg is more effective compared to 5 mg/kg. Lercanidipinine can be useful in the treatment of NSAID-induced gastric damage.


Subject(s)
Animals , Male , Rats , Stomach Ulcer/prevention & control , Dihydropyridines/therapeutic use , Protective Agents/therapeutic use , Stomach Ulcer/chemically induced , Indomethacin , Rats, Wistar , Disease Models, Animal
19.
Braz. arch. biol. technol ; 63: e20180626, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132199

ABSTRACT

Abstract Methotrexate (MTX) was shown to cause oxidative stress and liver damage. The objective was to investigate the possible protective effects of Matricaria Chamomilla L. (chamomile) extract with anti-oxidant and anti-inflammatory properties on the methotrexate-induced liver toxicity. Twenty four Wistar rats were divided into four groups. MTX group was injected intraperitoneally on days 7 and 14 with 20 mg/kg methotrexate. Groups CE200 (chamomile extract 200 mg/kg/day) and CE300 (chamomile extract 300 mg/kg/day) received the same dose of methotrexate added with chamomile extract orally for 15 days at 200 mg/kg and 300 mg/kg respectively and the last group was healthy control group. Results of biochemical analyses indicated serum liver biomarkers (aminotransferases), alkaline phosphatase (ALP), albumin, and liver content of anti-oxidant enzymes (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), reduced glutathione (GSH) and total anti-oxidant capacity (TAC) significantly increased (P <0.05-0.001) to normal in the CE treated groups compared to those of the MTX group. Serum bilirubin and hepatic malondialdehyde (MDA) levels significantly increased (P ˂0.001) in MTX group compared to those of the control group and decreased in CE200 and CE300 groups compared to those of the MTX group. Histopathological study showed inflammatory damage, necrotic cells and lipid infiltration in MTX group. In the groups treated with the chamomile extract, a significant improvement was observed in liver tissue in response to increased dose of the extract. In conclusion, chamomile extract administration could have a protective role in methotrexate-induced liver toxicity in rats through improving anti-oxidant defense system.


Subject(s)
Animals , Male , Rats , Plant Extracts/therapeutic use , Methotrexate/toxicity , Protective Agents/therapeutic use , Matricaria/chemistry , Liver/drug effects , Rats, Wistar
20.
Arq. gastroenterol ; 56(4): 333-338, Oct.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055177

ABSTRACT

ABSTRACT BACKGROUND: Indigofera suffruticosa Mill (Fabaceae) is abundant in northeastern Brazil and popularly used in the treatment of infectious and inflammatory processes. Several biological properties, such as anti-inflammatory, anticancer, antitumor, hepatoprotective and low toxicity, are reported for this plant. OBJECTIVE: This study investigated hepatoprotective activity and the antioxidant effect of methanolic extract of I. suffruticosa leaves (MEIS) on Swiss albino mice submitted to experimental models of acetaminophen-induced liver injury. METHODS: MEIS (50 mg/kg; p.o.) was standardized according to the LD50 and its hepatoprotective property on Swiss albino mice evaluated during a 7-day period. On the eighth day, the acetaminophen-induced hepatic injury was performed. Histomorphometric analysis of liver tissue, antioxidant activity and serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and bilirubin were measured. RESULTS: MEIS (50 mg/kg; p.o.) restored serum enzyme levels and results were close to those of positive control (silymarin) when compared to the negative control. Histopathological and histomorphometric analyzes confirmed MEIS hepatoprotective activity, showing reorganization of structural units of cells, nuclei and sinusoidal capillaries of hepatocytes, reducing the damage on liver tissue and increasing organ regeneration rate. MEIS showed high antioxidant potential at concentrations of 1000 and 500 µg/mL. CONCLUSION: This study suggests that MEIS has hepatoprotective activity and high antioxidant potential.


RESUMO CONTEXTO: Indigofera suffruticosa Mill (Fabaceae) é abundante no nordeste do Brasil e popularmente utilizada no tratamento de processos infecciosos e inflamatórios. Várias propriedades biológicas, como anti-inflamatório, anticâncer, antitumoral, hepatoprotetor e baixa toxicidade, são relatadas para esta planta. OBJETIVO: Este estudo investigou a atividade hepatoprotetora e o efeito antioxidante do extrato metanólico de folhas de I. suffruticosa (MEIS) em camundongos albinos suíços submetidos a modelos experimentais de lesão hepática induzida por paracetamol. MÉTODOS: O MEIS na dose de 50 mg/kg (via oral) foi padronizado de acordo com a LD50 e sua propriedade hepatoprotetora em camundongos albinos Swiss avaliados durante um período de sete dias. No oitavo dia, a lesão hepática foi induzida por paracetamol em todos grupos pre-tratados. Foram medidos os níveis sericos enzimaticos, alanina aminotransferase, aspartato aminotransferase e bilirrubina, análise histomorfométrica do tecido hepático e atividade antioxidante. RESULTADOS: O MEIS restaurou os níveis séricos de enzimas e os resultados foram próximos aos do controle positivo (silimarina) quando comparados ao controle negativo. As análises histopatológicas e histomorfométricas confirmaram a atividade hepatoprotetora do MEIS, mostrando reorganização das unidades estruturais das células, núcleos e capilares sinusoidais dos hepatócitos, reduzindo os danos no tecido hepático e aumentando a taxa de regeneração de órgãos. O MEIS apresentou alto potencial antioxidante nas concentrações de 1000 e 500 µg/mL. CONCLUSÃO: Este estudo sugere que I. suffruticosa tem atividade hepatoprotetora e alto potencial antioxidante.


Subject(s)
Animals , Male , Plant Extracts/administration & dosage , Analgesics, Non-Narcotic/toxicity , Protective Agents/administration & dosage , Indigofera/chemistry , Chemical and Drug Induced Liver Injury/prevention & control , Acetaminophen/toxicity , Aspartate Aminotransferases/blood , Bilirubin/blood , Alanine Transaminase/blood , Chemical and Drug Induced Liver Injury/etiology
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