Protective effect of Et-1 receptor antagonist bosentan on paracetamol induced acute liver toxicity in rats

Abstract

Paracetamol is one of the first rank drugs which cause hepatic damage during drug intoxications. Endothelin (ET) which is known as one of the most potent vasoactive agent has been shown to contribute in the pathophysiology of various diseases. We hypothesized that bosentan, which is a non-selective ET-1 receptor antagonist, can prevent liver damage. This study included 49 female rats. Groups; I: Healthy group, II: Paracetamol (2g/kg orally). Groups 3, 4 and 5 received NAC 140mg/kg (2 doses), BOS 45mg/kg and BOS 90mg/kg orally, respectively. 1h after administration of pretreatment drugs, Groups 3, 4, 5 were given paracetamol. VI: received BOS 90mg/kg. VII: received 140mg/kg NAC (2 doses). According to biochemical results, TNF-α, ALT and AST levels were statistically increased in the paracetamol group, these parameters were improved in the bosentan groups. Paracetamol administration decreased SOD activity, GSH level and increased level of MDA in the liver, while bosentan administration significantly improved these parameters. In immunohistochemical staining ET-1 receptor expression was excessively increased in paracetamol group, but not in bosentan groups when compared to healthy control. All these results suggest that bosentan exerted protective effects against experimentally induced paracetamol toxicity in liver.