A protective effect of pyrrolidine dithiocarbamate in a rat model of liver cirrhosis.

Nuclear factor kappa B (NF-kappaB) activation, proinflammatory cytokines, and reactive oxygen species have been implicated as mediators of liver injury and fibrogenesis. We have shown recently that pyrrolidine dithiocarbamate (PDTC), an antioxidant and inhibitor of NF-kappaB activation, was protective in a rat model of acute liver failure. The aim of the present study was to examine the efficacy of PDTC in a chronic rat model of thioacetamide (TAA)-induced hepatic fibrosis. Liver cirrhosis was induced by intraperitoneal injections of TAA (200 mg/kg) twice weekly for 12 weeks. Two groups of rats also received PDTC (either 20 or 60 mg/kg, i.p. for 12 weeks). TAA administration induced liver cirrhosis, which was inhibited by PDTC in a dose-dependent manner. The histopathologic score of fibrosis, the spleen weight, and hepatic hydroxyproline were significantly lower in the rats treated with TAA+PDTC compared with TAA only (P<0.001). The hepatic levels of thiobarbituric acid reactive substances and protein carbonyls after 12 weeks of treatment were also lower in the rats treated with TAA+PDTC (P=0.02 and 0.01, respectively), indicating reduced oxidative stress. Immunohistochemical studies and in situ hybridization demonstrated inhibition of stellate cell (alpha smooth muscle actin positive) activation, tissue inhibitor of metalloproteinase-2, and collagen alpha1(I) gene expression in the livers of the PDTC-treated rats. As determined by Northern blot analysis, PDTC had no inhibitory effect on collagen alpha1(I) gene expression in the rat hepatic stellate cells-T6 cells in vitro. PDTC inhibits the development of liver cirrhosis in TAA-treated rats. The mechanism of action is associated with decreased oxidative stress and hepatic necroinflammation.

Bruck R ，Schey R ，Aeed H ，Hochman A ，Genina O ，Pines M ... -  《LIVER INTERNATIONAL》

Prevention of liver cirrhosis in rats by curcumin.

Bruck R ，Ashkenazi M ，Weiss S ，Goldiner I ，Shapiro H ，Aeed H ，Genina O ，Helpern Z ，Pines M ... -  《-》

Curcumin ameliorates acute thioacetamide-induced hepatotoxicity.

Shapiro H ，Ashkenazi M ，Weizman N ，Shahmurov M ，Aeed H ，Bruck R ... -  《-》

Protective effect of pyrrolidine dithiocarbamate on liver injury induced by intestinal ischemia-reperfusion in rats.

Tian XF ，Yao JH ，Li YH ，Gao HF ，Wang ZZ ，Yang CM ，Zheng SS ... -  《Hepatobiliary & Pancreatic Diseases International》

Nuclear factor-kappaB inhibition by pyrrolidinedithiocarbamate attenuates gastric ischemia-reperfusion injury in rats.

El Eter E ，Hagar HH ，Al-Tuwaijiri A ，Arafa M ... -  《CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY》