Molsidomine prevents cisplatin-induced hepatotoxicity

Abstract

Background and aims: Despite its beneficial effects, cisplatin has considerable nephrotoxic, ototoxic, neurotoxic and hepatotoxic side effects. It has been documented that reactive oxygen radical species are involved with the pathophysiology of cisplatin-induced hepatotoxicity. Molsidomine (MOL) can exert antioxidant and anti-inflammatory effects. Therefore, the current study was planned to determine the effects of cisplatin on the liver oxidant/antioxidant system and the possible protective effects of (MOL) on liver toxicity.

Methods: Animals were divided into four groups as follows: (1) control; (2) MOL; (3) cisplatin and (4) MOL plus cisplatin group. Biochemical and histopathological evaluations were performed on the extracted liver tissue. Also, serum levels of serum aspartate transaminase (AST) and serum alanine transaminase (ALT) were determined.

Results: Our results clearly indicated that liver antioxidant enzyme activities and ALT levels were significantly decreased, whereas lipid peroxidation and neutrophil accumulation were increased in the cisplatin-treated animals (5 mg/kg single dose, i.p.) compared to the control rats. MOL treatment (4 mg/kg/day, i.p.) for 3 consecutive days provided a significant protection against cisplatin-induced hazardous changes in the liver tissue. Our histopathological findings including caspase-3 activity were also in accordance with the biochemical results.

Conclusions: We propose that MOL acts in the liver as a potent scavenger of free radicals, anti-inflammatory and anti-apoptotic effects to prevent the toxic effects of cisplatin, both at the biochemical and histopathological levels.

Keywords: Cisplatin; Liver; Molsidomine; Oxidative stress.