Prevention of hepatic cirrhosis in rats by hydroxyl radical scavengers.
OBJECTIVE
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 alpha1 (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.
Bruck
R
R
Department of Gastroenterology, The E. Wolfson Medical Center, Holon, Israel. rbruck@wolfson.health.gov.il
Shirin
H
H
Aeed
H
H
Matas
Z
Z
Hochman
A
A
Pines
M
M
Avni
Y
Y
D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000378:metabolism; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors*; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000473:pathology; D013441:Sulfinic Acids / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013853:Thioacetamide
D024042:Collagen Type I; D016166:Free Radical Scavengers; D013441:Sulfinic Acids; D013853:Thioacetamide; C053310:methanesulfinic acid; D017665:Hydroxyl Radical; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D006909:Hydroxyproline; D004121:Dimethyl Sulfoxide