Melatonin Reduces Radiation-induced Apoptosis Through Change of bax and bcl-2 Expression in Peripheral Blood Lymphocytes

Abstract

Background: The most important harmful effect of ionizing radiation is the production of free radicals. A correlation was demonstrated between free radicals and apoptosis. Melatonin might be a direct free radical scavenger. Melatonin's ability to modify the expression of bcl-2 and bax and apoptosis in peripheral blood lymphocytes in rats was studied. Materials and Methods: Rats received one total-body x-radiation dosage of 2 Gy either with or without prior treatment of melatonin at a dosage of 100 mg/kg body weight. The animals were grouped as follows: VC control (VC), 2 Gy irradiation (RT), 100 mg/kg melatonin + 2 Gy irradiation (MLT + RT), and 100 mg/kg melatonin (MLT). Animals were given intraperitoneal melatonin or an identical amount of vehicle alone 1 hour before radiation. Blood samples were collected 4, 24, and 72 hours after radiation to evaluate apoptotic lymphocytes through flow cytometric analysis using the Annexin V/PI assay, as well as to measure bcl-2 and bax expression via quantitative real-time PCR. Results: An elevation was noted in the RT group in the percentage of apoptotic lymphocytes compared to the VC group (P < 0.0001). In contrast, the MLT + RT group considerably reduced it compared to the RT group (P < 0.0001) in all periods. The decline in melatonin-induced apoptosis was for the bax downregulation, bcl-2 upregulation, and a lower ratio of bax to bcl-2. Conclusion: Melatonin can protect rat lymphocytes from x-radiation-triggered apoptosis by modulating bcl-2 and bax expression. Therefore, melatonin could serve as a potential radio-protective agent, making it a candidate for use alongside radiation in clinical trials.