Effectiveness of resveratrol as a hepatoprotector in a rat model of paracetamol-induced liver injury / Eficácia do resveratrol como hepatoprotetor em modelo de rato com lesão hepática induzida por paracetamol

Objective: Evaluate the effectiveness of resveratrol as a hepatoprotector in a rat model of paracetamol-induced liver injury and its biodistribution to understand its pharmacokinetics. Methodology: As an experimental approach, animals were divided into the test group with 4 subgroups and the control group with 4 subgroups. Animals of the "treated" group were subjected to resveratrol pre-treatment for eight days, followed by intoxication with a high dose of paracetamol on the 8th day. Animals were euthanized to collect the blood and liver tissue samples 24 and 72 h after the last administration. Hepatoprotective activity was evaluated through serum levels of glycogen and hepatic enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), histological and morphometric analysis of the liver tissue. For biodistribution analysis, different organs (organs, kidneys, heart and lungs) were collected and macerated, and resveratrol was quantified using high-performance liquid chromatography. Statistical analyses of morphometry, transaminases and alkaline phosphatase measurements, and biodistribution results were performed using GraphPad Prism® 3.0. Differences between groups were compared using ANOVA, followed by the Bonferroni test. Statistical significance was set at p < 0.05. Results: Resveratrol has a hepatoprotective action against acute intoxication by paracetamol, as evidenced by the histological decrease in necrosis and inflammatory foci, preservation of glycogen and other 1,2-glycols in zone 3, and reduction of serum ALT and AST levels. An increased presence of collagen was observed in acinar zones 1 and 3 with picrosirius red staining; therefore, quantification was performed in these regions showing smaller collagen areas in the R and RP groups than in the PC and NC groups Paracetamol caused a significant reduction in the resveratrol concentration in serum and the organs studied, indicating that the antioxidant activity of resveratrol is related to its hepatoprotective action. Conclusion: Resveratrol has hepatoprotective properties and can mitigate some of the liver damage caused by high doses of paracetamol, as indicated by changes in tissue characteristics and liver enzyme levels.

Objetivo: Avaliar a eficácia do resveratrol como hepatoprotetor em modelo de rato com lesão hepática induzida por paracetamol e sua biodistribuição para compreender sua farmacocinética. Metodologia: Como abordagem experimental, os animais foram divididos em grupo teste com 4 subgrupos e grupo controle com 4 subgrupos. Os animais do grupo "tratado" foram submetidos ao pré-tratamento com resveratrol durante oito dias, seguido de intoxicação com alta dose de paracetamol no oitavo dia. Os animais foram eutanasiados para coleta de amostras de sangue e tecido hepático 24 e 72 horas após a última administração. A atividade hepatoprotetora foi avaliada através dos níveis séricos de glicogênio e de enzimas hepáticas, como aspartato aminotransferase (AST), alanina aminotransferase (ALT) e fosfatase alcalina (ALP), análise histológica e morfométrica do tecido hepático. Para análise de biodistribuição, diferentes órgãos (órgãos, rins, coração e pulmões) foram coletados e macerados, e o resveratrol foi quantificado por cromatografia líquida de alta eficiência. Análises estatísticas de morfometria, medidas de transaminases e fosfatase alcalina e resultados de biodistribuição foram realizadas utilizando GraphPad Prism® 3.0. As diferenças entre os grupos foram comparadas por meio de ANOVA, seguida do teste de Bonferroni. A significância estatística foi estabelecida em p < 0,05. Resultados: O resveratrol tem ação hepatoprotetora contra a intoxicação aguda por paracetamol, evidenciada pela diminuição histológica da necrose e dos focos inflamatórios, preservação do glicogênio e outros 1,2-glicóis na zona 3 e redução dos níveis séricos de ALT e AST. Foi observada presença aumentada de colágeno nas zonas acinares 1 e 3 com coloração picrosirius red; portanto, foi realizada quantificação nessas regiões mostrando menores áreas de colágeno nos grupos tratados com resveratrol e resveratrol associado com paracetamol do que nos grupos controles positivo e negativo. O paracetamol causou redução significativa na concentração de resveratrol no soro e nos órgãos estudados, indicando que a atividade antioxidante do resveratrol está relacionada à sua ação hepatoprotetora. Conclusão: O resveratrol possui propriedades hepatoprotetoras e pode mitigar alguns dos danos hepáticos causados por altas doses de paracetamol, conforme indicado por alterações nas características dos tecidos e nos níveis de enzimas hepáticas.

Hepatoprotective effect of Lycopodium clavatum 30CH on experimental model of paracetamol-induced liver damage in rats.

INTRODUCTION: Homeopathic Lycopodium clavatum is indicated for disorders of the digestive system and its accessory organs, including atony of the liver and liver tissue failure. Tis suggests that it may have action on drug-induced hepatitis, as occurs in paracetamol overdose. PURPOSE: To evaluate the effectiveness of Lycopodium clavatum 30C (Lyc) as a hepatoprotector against liver damage experimentally induced by paracetamol (Pct) in Wistar rats. METHODOLOGY: Thirty animals subdivided into 6 groups were used. Animals from the treated groups were pretreated for 8 days with Lyc 30c (0.25 ml/day), receiving a dose of 3 g/kg of Pct on the 8th day. A positive control group received similar treatment, replacing Lyc 30c with 30% ethanol and a negative control received only 30% ethanol. After 24 and 72 h, the animals were sacrificed for tissue and blood sample collection. Subsequently, enzyme serum measurements indicative of liver damage (aspartate-aminotransferase (AST) and Alanine-aminotransferase (ALT)) and liver histological and morphometric analyses were performed. RESULTS: Pretreatment with Lyc 30c reduced hepatic lesions produced by Pct overdose as evidenced by a significant reduction (p < 0.05) in ALT levels in the LyP 24h-group (901.04 ± 92.05 U/l) compared to the respective control group (1866.28 ± 585.44 U/l), promoted a significant decrease in the number of acinar zone 1 affected by necrosis and inflammatory infiltration (15.46 ± 13.86 clr/cm(2) in LyP72 for 73.75 ± 16.60 clr/cm(2) in PC72), and inhibition of 1,2-glycol (glycogen) depletion in zone 3 (a significant reduction in Lyc 72 h group animals in comparison to the control group). Significant changes concerning the development of fibrosis or alterations in transaminase levels were not observed after 72 h. CONCLUSION: Lyc 30c exerted a moderate hepatoprotective effect on acute Pct-induced hepatitis, mainly shown by a histological decrease in necrosis and inflammatory foci, preserved glycogen and other 1,2-glycols in zone 3 and reduced serum levels of ALT and AST.