Protective Effects of Apocynin on Cisplatin-induced Hepatotoxicity in Rats

Despite it being a highly potent antineoplastic drug, cisplatin has important toxic adverse effects limiting its use such as nephrotoxicity, neurotoxicity and ototoxicity. It is thought that cisplatin-induced hepatotoxicity is caused by oxidative stress resulting from increased reactive oxygen species (ROS). Apocynin (APO) exerts its antioxidant effect by reducing ROS production via inhibition of NADPH oxidase. The present study intended to demonstrate effects of cisplatin on hepatic pro-oxidant/antioxidant systems and to investigate protective effects of APO against cisplatin-induced hepatotoxicity.

Rats were randomly assigned into four groups (n = 8 each): a) control group; b) single dose of cisplatin (5 mg/kg); c) APO group (20 mg/kg on three consecutive days; i.p.); and d) APO plus cisplatin group. Liver tissue was assessed in all groups by biochemical and histopathological means. Also, serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase levels were studied in all groups.

When cisplatin group was compared to controls, it was seen that lipid peroxidation product, total oxidant status and ALT levels were markedly increased, whereas superoxide dismutase and glutathione peroxidase levels were overtly decreased. APO therapy markedly prevented cisplatin-induced harmful changes in liver. Our histopathological findings such as central vein dilatation, perivenuler and periportal sinusoidal dilatation, parenchymal inflammation, vacuolar changes in hepatocytes, biliary duct proliferation and caspase-3 positive hepatocytes were in accordance with the biochemical changes.

In light of these results, it is our thought that APO has a protective role against cisplatin-induced hepatotoxicity at both biochemical and histopathological levels.