Hesperidin alleviates antitubercular drug induced oxidative stress, inflammation and apoptosis in rat liver

[摘要] Background: Drug induced hepatotoxicity is a serious health problem that leads to treatment interruption and change in the treatment regimen during the course of therapy. Isoniazid (H), Rifampicin(R) and pyrazinamide (Z) are the commonly used drugs for the treatment of tuberculosis but leads to undesirable side effects, such as hepatotoxicity. Hence the present study undertaken to investigate the hepatoprotective activity of Hesperidin (HDN) against Isoniazid, Rifampicin and Pyrazinamide induced hepatotoxicity.Methods: Wistar albino rats were randomly divided into four groups of six animals each. Isoniazid, Rifampicin, Pyrazinamide were used to induce Hepatotoxicity, Hesperidin 200mg/kg was given one hour prior administration of antitubercular drugs (HRZ), Silymarin 100mg/kg was used as a standard drug daily for 50 days.Results: Antitubercular drug induces hepatotoxicity was evident by increased in the levels of liver marker enzyme (AST, ALT, ALP & LDH) and also a significant rise in the level of LPO along with decline in the level of both enzymatic and non enzymatic antioxidant enzymes (SOD,CAT,GSH,VIT C and VIT E) . Moreover, antitubercular drug causes hepatic damage by inducing apoptotic death and inflammation in hepatic cells, manifested by an increase in the expression of Bax, caspase-3, caspase-9, NF-?B, IL- 10, TNF- ? and decrease in Bcl-2 expression. These results were further supported by the histopathological examination of liver. All these features of antitubercular drugs induced toxicity were reversed by the co-administration of Hesperidin.Conclusion: Therefore, our study favors the view that Hesperidin may be a useful modulator in alleviating antitubercular drug induced oxidative stress, inflammation and apoptosis.

[学科分类] 基础医学

[关键词] Reactive oxygen species(ROS);Isoniazid;Rifampicin;Pyrazinamide;Hesperidin;Hepatotoxicity.