The Protective Effects of Melatonin on Aluminum-Induced Hepatotoxicity and Nephrotoxicity in Rats

Aluminum (Al) is a ubiquitous element with known toxicity for both humans and animals. Herein, we aimed to investigate the potential role of melatonin (MEL) in hepatotoxicity and nephrotoxicity following aluminum chloride (AlCl(3)) treatment in rats. Adult male rats were treated with AlCl(3) (34 mg/kg bwt) for eight weeks. Exposure to AlCl(3) enhanced the serum activities of the liver transaminases (alanine aminotransferase and aspartate aminotransferase) and increased the level of bilirubin, in addition to the serum kidney function markers urea and creatinine. AlCl(3) intoxication boosted oxidative stress, as evidenced by increases in the levels of lipid peroxidation (LPO) and nitric oxide (NO) along with simultaneous decreases in the levels of glutathione (GSH), various antioxidant enzymes, and Nrf2 mRNA expression. MEL (5 mg/kg bwt) treatment repressed LPO and NO levels, whereas it augmented GSH content. The activities of the antioxidant enzymes GPx, SOD, CAT, and GR were also restored concomitantly when MEL was administered before AlCl(3). MEL also suppressed the apoptotic effect of AlCl(3) by enhancing Bcl-2 protein expression in the liver and kidney and decreasing the expression levels of proinflammatory cytokines. Histopathological findings in the liver and kidney tissues confirmed the beneficial effect of MEL against AlCl(3) toxicity. These findings indicate that MEL prevents AlCl(3) toxicity by enhancing the antioxidant defense system.