IntroductionMany clinical conditions, including strictures of the bile duct, gallstone complications of pancreatitis, or biliary surgery, are cited among etiologies that lead to a decrease in biliary flow, causing cholestasis (1). Cholestasis leads to acute hepatic injury and results in progressive fibrosis (2). The production of free oxygen radicals has been suggested to play an important role in the pathogenesis of cholestasis. One of the significant endpoints leading to liver damage arising from cholestasis is considered to be intrahepatic accumulation of toxic bile salts and inflammatory cells (3). A validated experimental model of acute cholestasis in rats can be presented by bile duct ligation (BDL) (4).Lipid peroxidation may result from the excessive production of reactive oxygen species (ROS), which may then interrupt the integrity of the cellular membranes and cause further hepatic injury in cholestasis (5-7). In cholestasis, the decline in the activity of glutathione peroxidase (GSH-Px), as well as the decline in reduced glutathione (GSH), may damage the antioxidant defense system (7). Altered gene expression and DNA base damage are the results of ROS; these may lead to the development of cancer and mutation (8).Useful effects of antioxidants in cholestasis have been reported in several experimental models (9). Being a natural antioxidant carotenoid, lycopene is suggested to be one of the most powerful antioxidants (10). Animal studies have indicated a large margin of safety for lycopene. An oral 90-day toxicity study in Wistar albino rats demonstrated the daily NOAEL of lycopene to be 586 Background/aim: Lycopene, which is suggested to be a potent antioxidant, may play a protective role in diseases related to oxidative stress. In order to understand the effects of lycopene in the pathogenesis of cholestasis, we investigated the effects of lycopene on oxidative stress parameters and DNA damage induced by experimental biliary obstruction in the liver tissues and the lymphocytes of Wistar albino rats.
Materials and methods:The animals were randomized into 3 groups. The sham group was subjected to a sham operation, the BDL group was subjected to bile duct ligation (BDL), and the BDL+L group was subjected to BDL and treated with 10 mg/kg body weight of lycopene. After 7 days of treatment, the liver functions, oxidative stress parameters, and DNA damage were evaluated.
Results:The lycopene treatment significantly ameliorated the liver function parameters in BDL rats. It significantly reduced malondialdehyde and nitric oxide levels and enhanced reduced glutathione levels and catalase, superoxide dismutase, and glutathione S transferase activities in the BDL rats. The lycopene treatment also decreased DNA damage as assessed by comet assay in the lymphocytes and hepatocytes of the BDL rats.
Conclusion:These results suggest that lycopene might have protective effects on acute cholestasis.