Bruck, R., Department of Gastroenterology, E. Wolfson Medical Center, Holon 58100, Israel
Shirin, H., Department of Gastroenterology, E. Wolfson Medical Center, Holon 58100, Israel
Aeed, H., Department of Gastroenterology, E. Wolfson Medical Center, Holon 58100, Israel
Matas, Z., Department of Biochemistry, E. Wolfson Medical Center, Holon 58100, Israel
Hochman, A., Department of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Avni, Y., Department of Gastroenterology, E. Wolfson Medical Center, Holon 58100, Israel

Background/Aims: Reactive oxygen species and oxidative stress were implicated in hepatic stellate cell activation and liver fibrosis. The aim of the present study was to examine whether the administration of free radical scavengers in vivo would prevent experimentally-induced hepatic cirrhosis in rats. Methods: Cirrhosis was induced by administration of thioacetamide (TAA; 200 mg/kg, i.p.) twice/week, for 12 weeks. Rats were treated concurrently with either dimethylsulfoxide (DMSO; 4 g/kg, s.c. or p.o.) or dimethylthiourea (DMTU; 200 mg/kg i.p.) three times a week. Results: Liver fibrosis (histopathological score, spleen weight, and hepatic hydroxyproline) was abolished in rats treated with TAA and either DMSO or DMTU (P < 0.001). Accordingly, the hepatic expression of alpha smooth muscle actin, tissue inhibitor of metalloproteinase 2 and collagen α1 (I) gene were inhibited. The hepatic level of methane-sulfinic acid (produced by the interaction of DMSO with hydroxyl radicals) was increased in rats treated with TAA + DMSO (P = 0.0005) and decreased after pretreatment of these rats with DMTU (P = 0.008). However, the hepatic levels of malondialdehyde, lipid peroxides and protein carbonyls were not lower in the DMSO- and DMTU-treated groups. Conclusions: The administration of free radical scavengers prevented the development of TAA-induced liver cirrhosis probably associated with decreased oxidative stress. © 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.