Ameliorative effect of diazepam against ethanol-induced mitochondrial disruption in brains of the mice

Abstract

Brain oxidative damage and neurodegeneration by ethanol (ETH) are considered as important factors that triggered by oxidative stress. Recently, the abuse of diazepam (DZM) has increased by alcoholism-addicted patients. The present study evaluated the effects of combination treatment of ETH with DZM on oxidative damage induced in brain mitochondria of the mice. Only ETH (0.3, 0.6, and 2.5 g / kg) and ETH+ DZM (2.5 mg / kg) were administered intraperitoneally (ip) to the mice. Pathological changes and oxidative stress biomarkers including ROS, lipid peroxidation, carbonyl protein, mitochondrial function, and glutathione content were evaluated in brain mitochondria after 42 days. Results indicated that co-treatment of DZM and ETH significantly reduced mitochondrial toxicity, oxidative damage, pathological changes and increased level of glutathione. Subchronic ETH administration induced brain oxidative damage, mitochondrial disruption, and serious damage to the brain cells. Whereas, combination treatment improved oxidative damage, mitochondrial function, and pathological changes in brain cells after intoxication by ETH. These findings suggest antioxidant effect of DZM in combination with ETH and can be considered in reducing oxidative stress and mitochondrial damage attenuation in the brain. Combination therapy may be a better therapeutic candidate for prevention of brain oxidative damage induced by ETH.