Curcumin ameliorates acute thioacetamide-induced hepatotoxicity

Background and Aim: Increased production of reactive oxygen species and nitric oxide and activation of nuclear factor κ B are implicated in the pathogenesis of various liver diseases, including fulminant hepatic failure. Curcumin is a naturally occurring anti-oxidant that reduces oxidative stress and inhibits nuclear factor κ B and nitric oxide formation. The aim of the present study is to assess curcumin's therapeutic potential in acute thioacetamide hepatotoxicity, a rat model of fulminant hepatic failure. Methods: Fulminant hepatic failure was induced by two intraperitoneal (i.p.) injections of 300 mg/kg thioacetamide (TAA) at 24-h intervals. The experimental groups received a low-dose (200 mg/kg per day, i.p.) or a high-dose (400 mg/kg per day) of curcumin, initiated 48 h prior to the first TAA injection. A fourth group was administered neither TAA nor curcumin and served as a control. Results: The survival rate was higher in both curcumin-treated groups compared to the TAA only treated group. Biochemical parameters of liver injury, blood ammonia and hepatic necroinflammation were lower in the low-dose curcumin group compared to TAA controls, and were further reduced in the high-dose group (P < 0.05 and P < 0.01, respectively). Curcumin treatment also reduced the TAA-induced elevated hepatic levels of thiobarbituric acid-reactive substances (TBARS), and inhibited the nuclear binding of nuclear factor κ B (NFκB) and inducible nitric oxide (iNOS) protein expression. Conclusions: Curcumin improved survival and minimized oxidative stress, hepatocellular injury and hepatic necroinflammation, NFκB binding and iNOS expression in a rat model of FHF. These findings support the role of ROS, NFκB and iNOS in mediating liver insult due to TAA, and that of curcumin as a hepato-protectant.