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 have shown that TGF-β, through upregulation of pro-oxidant enzymes such as NOX۲ and NOX۴, promotes continuous ROS production and accumulation of fibrosis. Objective: In present study, we aimed to evaluate the expression of NOX۲ and NOX۴ 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 ۲۰ rats (۵ in each) were used as follows; G۱: control; G۲: melatonin; G۳: radiation; G۴: radiation + melatonin. ۱۰۰ mg/kg of melatonin was administrated before irradiation of heart tissues with ۱۵ Gy gamma rays. ۱۰ weeks after irradiation, heart tissues were collected for real-time PCR. Results: Results showed a significant increase in the expression of TGF-β, Smad۲, NF-kB, NOX۲ and NOX۴. The upregulation of NOX۲ was more obvious by ۲۰-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-NOX۴ and TGF-β-NOX۲ pathways. Melatonin, through modulation of these genes, may be able to alleviate radiation-induced chronic oxidative stress and subsequent consequences.

کلیدواژه ها:

Radiation ، Melatonin ، Heart ، NADPH Oxidase ۲ ، NADPH oxidase ۴