Protective effect of melatonin against chronic cadmium-induced hepatotoxicity by suppressing oxidative stress, inflammation, and apoptosis in mice

Abstract

Cadmium (Cd) is a widespread environmental heavy metal pollutant that has high toxicity to human health. Cd accumulates in the liver and results in oxidative stress and inflammatory reactions. Melatonin (MT), a hormone exhibiting strong antioxidative properties, has been proved to have hepatoprotective effect against both acute and chronic liver injury. However, the molecular mechanism underlying MT's hepatoprotective effect against Cd-induced liver injury remain not fully understood. In this study, the potential protective effect of MT on Cd-induced hepatic injury was investigated. Adult male C57BL/6 mice were randomly divided into four groups: control, CdCl2, MT, and CdCl2 plus MT groups. Animals were daily treated with either CdCl2 (5 mg/kg) or MT (10 mg/kg) or both through intragastric administration for 30 consecutive days. Serum enzymatic analysis indicated that treatment mice with Cd significantly increased AST, ALT, LDH and ALP levels, by contrast, MT treatment resulted in significant decreases of AST, ALT, LDH and ALP levels in the serum of Cd treated mice. By biochemical analysis, it was found that MT treatment significantly increased the activities of SOD, GSH, GST, CAT and GR, while significantly decreased the contents of MDA in the liver tissue of Cd treated mice. Moreover, MT treatment also suppressed the Cd-induced inflammation by reducing the inflammatory mediators, including IL-1β, IL-6, TNF-α and iNOS. Furthermore, MT treatment ameliorated the Cd-induced histopathological variations of liver tissue, which was confirmed by the biochemical and molecular data. It is clear from the results of this study that MT exerts hepatoprotective effect by improving the redox state, suppressing inflammatory reaction and cell apoptosis as well as ameliorating the performance of liver tissue histopathology, which is eventually reflected by the improvement of liver function in mice.