Melatonin exerts a neuroprotective effect against γ-radiation-induced brain injury in the rat through the modulation of neurotransmitters, inflammatory cytokines, oxidative stress, and apoptosis

Abstract

The current study aimed to investigate the ameliorative effect of melatonin (MLT) against brain injury in rats undergoing whole-body exposure to γ-radiation. Male Wistar rats were whole-body exposed to 4-Gy γ-radiation from a cesium-137 source. MLT (10 mg/kg) was orally administrated 30 minutes before irradiation and continued once daily for 1 and 7 days after exposure. In the irradiated rats, the plasma levels of glutamate were increased, while the gamma-aminobutyric acid (GABA) levels were decreased, and MLT improved the disturbed glutamate and GABA levels. These effects paralleled an increase in pro-inflammatory cytokines (IL-1b, IL-6, and TNF-a) and C-reactive protein as well as a decrease in IL-10 in the plasma of the irradiated rats. MLT treatment markedly reduced these effects, indicating its anti-inflammatory impact. Immunohistochemical studies demonstrated a remarkable upregulation of caspase-3 and P53 expression, indicating the increased apoptosis in the brain of irradiated rats. MLT significantly downregulated the expression of these parameters compared with that in the irradiated rats, indicating its anti-apoptotic effect. Oxidative stress is developed in the brain as evidenced by increased levels of malondialdehyde; decreased activities of superoxide dismutase, catalase, and glutathione peroxidase; and decreased content of glutathione in the brain. MLT remarkably ameliorated the development of oxidative stress in the brain of the irradiated rats indicating its antioxidant impact. The histopathological results were consistent with the biochemical and immunohistochemical results and showed that MLT remarkably protected the histological structure of brain tissue compared with that in the irradiated rats. In conclusion, MLT showed potential neuroprotective properties by increasing the release of neurotransmitters, antioxidants, and anti-inflammatory factors and reducing pro-inflammatory cytokines and apoptosis in the brain of irradiated rats. MLT can be beneficial in clinical and occupational settings requiring radiation exposure; however, additional studies are required to elucidate its neuroprotective effect in humans.

Keywords: Antioxidants; Brain,; Inflammatory cytokines,; Ionizing radiation,; Melatonin,; Neurotransmitters,; Oxidative stress,.