Heroin-Induced Hepatotoxicity: Involved Oxidative Stress

Abstract

Chronic opiate intoxication has been shown to cause various pathologic changes in the liver almost in 100% of cases. Our aim is to find out the role of oxidative stress in hepatoxicity induced by heroin. Methods: A dose-increasing method was used to develop the heroin-dependent model in mice, the content of malondialdehyde (MDA) were measured by thiobarbituric acid (TBA) method, protein carbonyl by DNPH reagent, reduced glutathione (GSH) by DTNB method and percentage of cell with damaged DNA by comet method, and the activity of alanine aminotransferase (ALT) by commercial kit in hepatocytes of heroin administered mice. Coefficient of linear pair wise regression was used to evaluate the correlation between oxidative damage and hepatotoxicity induced by heroin. Results: The oxidative damaged products, MDA, protein carbonyl and the percentage of cells with damaged DNA increased in hepatocytes of heroin administered mice, while the antioxidant enzyme and substances, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as well as the content of GSH decreased, on the other hand, the hepatoxic index, activity of ALT in serum of heroin administered mice elevated remarkably. Positive correlations between ALT activity and contents of MDA (r=0.5442, n=15) and carbonyl (r=0.86, n=15) in the mice liver were found , while the correlative between ALT activity of in serum and GSH in hepatocytes is negative (r=- 0.6648, n=15). However, there is no close correlation between ALT activity and DNA damage. Conclusions: Increases oxidative damaged DNA, protein and lipid with decrease of antioxidants activity implied that there was a seriously oxidative stress in mice liver induced by heroin. Oxidative stress may cause hepatotoxicity.