Harmine Mitigates Liver Injury Induced by Mercuric Chloride via the Inhibition of Oxidative Stress

Document Type : Original paper

Authors

1 Department of Anatomy, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

2 Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

3 Department of Biochemistry, Medical Faculty, Saveh Branch, Islamic Azad University, Saveh, Iran.

Abstract

Background and objective: The mercury-induced liver pathogenesis is mainly mediated by oxidative stress. The aim of the current study was to evaluate the possible ameliorative effect of harmine, a natural compound, on liver toxicity induced by mercury chloride (HgCl2). Methods: Forty-two male Balb/c mice were randomly divided into six groups (n = 7): Control, HgCl2 (0.5 mg/kg), harmine (20 mg/kg), and HgCl2 (0.5 mg/kg) + harmine (5, 10, or 20 mg/kg). The mice received treatments once per day for two weeks. After this period, the blood and tissue samples were collected for analyses. Results: HgCl2 caused a significant increase in levels of hepatic enzymes alanine aminotransferase, aspartate transaminase, and alkaline phosphatase; while harmine ameliorated these effects. Harmine in HgCl2-intoxicated mice, showed protective effects as evidenced by the increase in liver relative weight to body as well as the diameter of central vein in the co-treated group. Serum levels of malondialdehyde and nitric oxide increased in HgCl2, while they were declined in harmine co-treated groups compared to HgCl2 group. The serum level of superoxide dismutase and total antioxidant capacity improved following harmine treatment in the co-administrated group compared to HgCl2 group. Moreover, gene expression analysis demonstrated that harmine treatment improved the HgCl2-induced decreasing of Ho-1, Nrf2, Hqo1, and Trx1. The histopathological examination confirmed the protective effects of harmine. Conclusion: Mercury can induce toxicity by elevation of oxidative stress in the liver and harmine attenuates hepatic injury induced by HgCl2, at least in part, through its antioxidant activities.

Keywords


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