Portal de Periódicos da CAPES

Cimetidine prevents and partially reverses CCl 4 ‐induced liver cirrhosis

1994; Wiley; Volume: 14; Issue: 2 Linguagem: Inglês

10.1002/jat.2550140205

1099-1263

Pablo Muriel, Elvia Mera, Carlos Castillo, Marisabel Mourelle,

Pharmacogenetics and Drug Metabolism

Abstract Liver injury produced by CCl 4 depends on its metabolism by the liver cytochrome P 450 enzyme system to a highly reactive intermediate (CCl 3 ·). Cimetidine impairs cytochrome P 450 and stimulates regenerative processes acting on DNA synthesis. This work was performed to investigate whether cimetidine may prevent CCl 4 ‐induced liver cirrhosis. Male Wistar rats were used: animals in group 1 received CCl 4 (0.04 g per 100 g, i.p.) three times a week for 8 weeks; group 2 was treated with CCl 4 plus cimetidine (120 mg kg −1 , p.o.) three times a week for 8 weeks; group 3 received CCl 4 for 8 weeks and then cimetidine for 4 weeks. Alkaline phosphatase, γ‐glutamyl transpeptidase (γ‐GTP) and alanine aminotransferase (ALT) activities, as well as protein and bilirubin, were measured in serum; collagen and lipoperoxidation were quantified in liver. Intoxication with CCl 4 increased ( P < 0.05) serum activities of alkaline phosphatase, γ‐GTP and ALT, and bilirubin concentration; liver collagen and lipoperoxidation were also increased. Cimetidine treatment prevented or reverted the increases in the three enzyme activities and in bilirubin content and the fall in proteins. It is worth noting that cimetidine co‐treatment completely prevented both the increase in collagen content and the lipid peroxidation. The protective effect of cimetidine can be attributed to a reduction in cytochrome P 450 . However, it could also stimulate regenerative processes.