The effect of serotonin reuptake inhibitors on hepatic injury induced by carbon tetrachloride

Abstract

The aim of the present study was to investigate the effect of several drugs acting on serotonergic neurotransmission on the development of hepatocellular injury caused by carbon tetrachloride (CCl4) in rats. Liver damage was induced in rats by administration of CCl4 (2.8 ml/kg in olive oil, orally). Sertraline, citalopram, or fluvoxamine were administered orally once daily in association with CCl4 and for 1 week thereafter. Sibutramine was administered 1 week prior to the toxic agent and for 3 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. In CCl4-treated rats, sertraline (10, 20 mg/kg) reduced serum alanine aminotransferase (ALT) levels by 41.8% and 53.4%, respectively, compared to controls. Serum aspartate aminotransferase (AST) levels decreased by 37.4% and 58.2%, respectively, while alkaline phosphatase (ALP) decreased by 40.5% and 59.3%, respectively. Treatment with citalopram (5, 10, 20 mg/kg) reduced serum ALT levels by 29.8%, 35.6%, and 43.8%, AST levels by 24.2%, 29.9%, and 43%, and ALP by 17.8%, 35%, and 48.9%, respectively. Fluvoxamine (5, 10, 20 mg/kg) dose-dependently reduced the elevation of ALT levels by 42.6%, 49.9%, and 51.9%, AST levels by 40.2%, 44.6%, and 61.6%, and ALP by 8.3%, 46.8%, and 52.7%, respectively. Given as a pretreatment, sibutramine (5, 10, 20 mg/kg) reduced serum ALT levels by 52.1%, 52.2%, and 57.5%, AST levels by 53.6%, 58.4%, and 59.4%, and ALP by 46.8%, 67.6%, and 72.2%, respectively. Histopathological and histochemical examinations also indicated that CCl4-induced liver injury was less severe after treatment with the test drugs than in the CCl4 control groups. It is concluded that the administration of drugs with serotonin reuptake inhibitory properties is associated with a reduction in experimental liver injury induced by CCl4.