Melatonin alleviates aluminium chloride-induced immunotoxicity by inhibiting oxidative stress and apoptosis associated with the activation of Nrf2 signaling pathway.

The present study aimed to investigate whether melatonin (MT) treatment can attenuate immunotoxicity induced by aluminum chloride (AlCl3) in rat spleen. Forty-eight healthy male Wistar rats were randomly allocated and treated with AlCl3 and/or MT. Rats were orally administered with AlCl3 for 90 days, from 61st days, rats were injected intraperitoneally with MT for 30 days. Firstly, we found that MT relieved the AlCl3-induced immunosuppression by improving spleen structural damage, CD3+ and CD4+ T lymphocyte subsets, IL-2 and TNF-α mRNA expressions and decreasing CD8+ T lymphocyte subsets. Secondly, MT attenuated the AlCl3-induced oxidative stress in rat spleen by decreasing the levels of ROS and MDA, while increasing the activities of SOD and CAT. Thirdly, MT relieved the AlCl3-induced apoptosis in rat spleen by increasing the MMP and Bcl-2 mRNA and protein expressions, while decreasing apoptosis rates, activity of Caspase-3 and pro-apoptotic gene expression. Finally, MT increased Nrf2 nuclear translocation, and Nrf2 target genes (HO-1, NQO1, SOD1 and CAT) mRNA expressions in the spleen of AlCl3-exposed rat. These results suggest that MT may alleviate AlCl3-induced immunotoxicity by inhibiting oxidative stress and apoptosis associated with the activation of Nrf2 signaling pathway, which could lay the foundation for the treatment of AlCl3 immunotoxicity.