Pyrrolidine dithiocarbamate protects against thioacetamide-induced fulminant hepatic failure in rats

Abstract Background/Aims : Reactive oxygen species and nuclear factor kappa B (NF- κ B) activation have been implicated in the pathogenesis of cell injury in experimental models of liver damage. The aim of the present study was to examine whether pyrrolidine dithiocarbamate (PDTC), an anti oxidant and inhibitor of NF- κ B activation, would prevent hepatic damage induced in a rat model of thioacetamide (TAA)-induced liver failure. Methods : Fulminant hepatic failure was induced in the control and treatment groups by two intraperitoneal injections of TAA (either 300 or 400 mg/kg) at 24-h intervals. In the treatment groups, rats were treated also with PDTC (60 mg/kg/24 h, i.p.), initiated 24 h prior to TAA. Results : Liver enzymes, blood ammonia, and hepatic levels of thiobarbituric acid reactive substances ( P P P κ B activation, 2 and 6 h after TAA administration, was inhibited by PDTC. Conclusions : In a rat model of fulminant hepatic failure, the administration of PDTC attenuated liver damage and improved survival. This effect may be due to decreased oxidative stress and inhibition of NF- κ B activation.