Prevention of hepatic cirrhosis in rats by hydroxyl radical scavengers

Rafael Bruck, Haim Shirin, Hussein Aeed, Zipora Matas, Ayala Hochman, Mark Pines, Yona Avni

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)457-464
Number of pages8
JournalJournal of Hepatology
Volume35
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Dimethylsulfoxide
  • Hydroxyl radical scavengers
  • Liver cirrhosis
  • Thioacetamide

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