modulation of radiation-induced nadph oxidases in rat’s heart tissues by melatonin

Background: experimental studies have shown that infiltration of inflammatory cells as well as upregulation of some cytokines play a central role in the development of late effects of ionizing radiation in heart tissues. evidences have shown that an increased level of tgf-β has a direct correlation with late effects of exposure to ionizing radiation such as chronic oxidative stress and fibrosis. recent studies haveshown that tgf-β, through upregulation of pro-oxidant enzymes such as nox2 and nox4, promotes continuous ros production and accumulation of fibrosis.objective: in present study, we aimed to evaluate the expression of nox2 and nox4 signaling pathways as well as possible modulatory effects of melatonin on the expression of these genes.material and methods: in this experimental study, four groups of 20 rats (5 in each) were used as follows; g1: control; g2: melatonin; g3: radiation; g4: radiation + melatonin. 100 mg/kg of melatonin was administrated before irradiation of heart tissues with 15 gy gamma rays. 10 weeks after irradiation, heart tissues were collected for real-time pcr. results: results showed a significant increase in the expression of tgf-β, smad2, nf-kb, nox2 and nox4. the upregulation of nox2 was more obvious by 20-fold compared to other genes. except for tgf-β, melatonin could attenuate the expression of other genes. conclusion: this study indicated that exposure of rat’s heart tissues to radiation leads to upregulation of tgf-β-nox4 and tgf-β-nox2 pathways. melatonin, through modulation of these genes, may be able to alleviate radiationinduced chronic oxidative stress and subsequent consequences.