BACKGROUND/AIMS: Reactive oxygen species and nuclear factor kappa B (NF-kappaB) 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-kappaB 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<0.001) and protein carbonyls (P<0.05) were significantly lower in rats treated with PDTC compared to TAA only. Liver histology and the survival rate in the PDTC-treated rats were also improved (P<0.01 compared to TAA only). NF-kappaB 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-kappaB activation.
BACKGROUND/AIMS: Reactive oxygen species and nuclear factor kappa B (NF-kappaB) 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-kappaB 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<0.001) and protein carbonyls (P<0.05) were significantly lower in rats treated with PDTC compared to TAA only. Liver histology and the survival rate in the PDTC-treated rats were also improved (P<0.01 compared to TAA only). NF-kappaB activation, 2 and 6 h after TAA administration, was inhibited by PDTC. CONCLUSIONS: In a rat model of fulminant hepatic failure, the administration of PDTCattenuated liver damage and improved survival. This effect may be due to decreased oxidative stress and inhibition of NF-kappaB activation.
Authors: Felipe A Pinho-Ribeiro; Victor Fattori; Ana C Zarpelon; Sergio M Borghi; Larissa Staurengo-Ferrari; Thacyana T Carvalho; Jose C Alves-Filho; Fernando Q Cunha; Thiago M Cunha; Rubia Casagrande; Waldiceu A Verri Journal: Inflammopharmacology Date: 2016-05-09 Impact factor: 4.473