Abstract
The antituberculosis drug-induced hepatotoxicity is a leading cause of liver injury in many countries. The current study aimed to investigate the possible protective effects of the isoquinoline alkaloid berberine against isoniazid (INH)-induced hepatotoxicity in rats. The experimental rats received 100 mg kg(-1) b.wt. INH and concurrently administered berberine at doses of 25 and 50 mg kg-1 orally for 45 days. To evaluate the hepatoprotective effects of berberine, serum markers of the liver function, serum pro-inflammatory cytokines and liver oxidant/antioxidant biomarkers were assayed. In addition, gene expression levels of inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-kappa B) and peroxisome proliferator-activated receptor gamma (PPAR gamma) were determined. INH induced hepatic damage evidenced by the significantly elevated serum transaminases, serum pro-inflammatory cytokines and liver lipid peroxidation and nitric oxide levels. Consequently, serum albumin, liver glutathione and activities of the antioxidant enzymes were significantly declined. Further, INH administration produced a significant upregulation of liver iNOS and NF-kappa B and downregulation PPAR gamma mRNA expressions. Concurrent supplementation of berberine restored the altered markers to an almost normal state, in a dose-dependent manner. In conclusion, Berberine protects against INH-induced oxidative stress and inflammation leading to liver injury. The protective effects of berberine can be attributed to its ability to upregulate PPAR gamma and subsequently suppress NF-kappa B, iNOS and release of the pro-inflammatory cytokines.