Alcohol-induced oxidative/nitrosative stress alters brain mitochondrial membrane properties

Abstract

Chronic alcohol consumption causes numerous biochemical and biophysical changes in the central nervous system, in which mitochondria is the primary organelle affected. In the present study, we hypothesized that alcohol alters the mitochondrial membrane properties and leads to mitochondrial dysfunction via mitochondrial reactive oxygen species (mROS) and reactive nitrogen species (RNS). Alcohol-induced hypoxia further enhances these effects. Administration of alcohol to rats significantly increased the mitochondrial lipid peroxidation and protein oxidation with decreased SOD2 mRNA and protein expression was decreased, while nitric oxide (NO) levels and expression of iNOS and nNOS in brain cortex were increased. In addition, alcohol augmented HIF-1α mRNA and protein expression in the brain cortex. Results from this study showed that alcohol administration to rats decreased mitochondrial complex I, III, IV activities, Na(+)/K(+)-ATPase activity and cardiolipin content with increased anisotropic value. Cardiolipin regulates numerous enzyme activities, especially those related to oxidative phosphorylation and coupled respiration. In the present study, decreased cardiolipin could be ascribed to ROS/RNS-induced damage. In conclusion, alcohol-induced ROS/RNS is responsible for the altered mitochondrial membrane properties, and alcohol-induced hypoxia further enhance these alterations, which ultimately leads to mitochondrial dysfunction.

Energy Drink Induced Lipid Peroxidation and Oxidative Damage in Rat Liver and Brain When Used Alone or Combined with Alcohol

“…It is well known that ethanol consumption increases the production of ROS and enhances oxidative damage in many tissues (Jing and others ; Reedy and others ). However, data on the effects of alcohol exposure on SOD, CAT, and GSH‐Px activity are discordant, with results having been reported as increase, no change, or decrease (Grasselli and others ).…”

Chronic Ethanol Exposure during Adolescence in Rats Induces Motor Impairments and Cerebral Cortex Damage Associated with Oxidative Stress

“…In cerebral cortex, chronic intake of alcohol alters cell membrane fluidity probably due to oxidative stress as indicated by increased nitrite and lipid peroxidation levels, enhanced presence of nitric oxide synthase and decreased superoxide dismutase [59]. However, all these effects were described for adult brains, and deleterious consequences for the developing brain with chronic intoxication from adolescence to adult age remains unknown.…”

The Role of Oxidative Stress in Cerebral Aneurysm Formation and Rupture

“…Alcohol increases the risk of aneurysm rupture independently of cigarette smoking, age, and history of hypertension [72, 73]. Accrued data suggest that free radicals produced by alcohol exposure in the central nervous system play important roles in neuroinflammation and neurodegenration [74–76]. Alcohol especially at levels attained in heavy drinkers was shown to affect human brain endothelial cells and the permeability of the blood-brain barrier through ROS formation [74, 77, 78].…”