Anti-apoptotic and antioxidant effects of melatonin protect spleen of whole body gamma-irradiated male Sprague-dawleny rats

Abstract

Background: Spleen is the largest lymphatic organ that is seriously affected during irradiation. Radiation exposure reduces both of spleen size and weight; that in turn decreases the numbers of immune cells. Melatonin is an effective free radicals scavenger. Therefore, this study aimed to evaluate the effects of melatonin on both blood and spleen of whole body gamma-irradiated male Sprague dawley rats. Materials and methods: Animals were intraperitoneally injected with 100 mg/kg melatonin prior to radiation exposure by 30 minutes. Experimental groups were group I: control rats, group II: irradiated rats, group III: melatonin administrated unirradiated rats and group IV: melatonin administrated irradiated rats. Blood and spleen samples were collected 24 hours post irradiation for biochemical, immunological and blastogenesis measurements. Apoptosis, pro- and anti-apoptotic proteins of spleen cells were measured by flow cytometry techniques. Results: Melatonin significantly upregulated the activities of superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT); and reduced malondialdehyde (MDA). It down regulated the expression of pro-apoptotic proteins (p53, Bax, caspase -3 and caspase-8) and up regulated the expression of anti-apoptotic protein Bcl-2 in spleen cells; that in turn reduced the radiation-induced apoptosis. Levels of pro-inflammatory cytokines (TNF-alpha, IFN-gamma and IL-1 beta) were significantly reduced in group IV. Blastogenesis assay showed that melatonin protects PBMC and spleen B lymphocytes and stabilized their proliferation. Conclusion: Melatonin administration prior to whole body gamma-radiation successfully protected rat's spleen from the consequences of radiation exposure. This was due to its free radicle scavenger nature, its reduction of lipid peroxidation and its anti-apoptotic effects.