[The action of oxidative stress induced by ethanol on the central nervous system (CNS)]

Abstract

The brain is an organ which metabolically consumes about 20% of the total oxygen received by the organism. This causes the generation of free radicals, especially in the presence of some xenobiotics, such as ethanol. In order to prevent free radical-induced cellular damage, the organism developed a defense mechanism, the antioxidative system. The content of both exogenous and endogenous antioxidants in the central nervous system (CNS) is very small in comparison with that of other tissues, which in relation to the high level of polyunsaturated fatty acids (PUFAs) makes the CNS exceptionally susceptible to free-radical damage. The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) are present in the CNS i.e. in the cortex, cerebellum, hypothalamus, striatum, and spinal cord, where they are responsible for the brain's basic functions, both physical and cognitive. Moreover, the highest activity of these enzymes is observed in neurons and/or glial cells. The activity of antioxidant enzymes is significantly changed in the CNS of animals chronically intoxicated with ethanol. The decrease in these activity may indicate at oxidative modification of the enzymatic proteins caused by free radicals which are generated during ethanol and acetaldehyde metabolism. It may also be caused by the decrease in the synthesis rate of these enzymes. However, the increase in the activity of antioxidant enzymes may often be explained as an adaptive reaction to an excess production of free radicals. The catalase is an exception in this respect because the decrease in its activity is related to the enhancement of protein synthesis. Ethanol intoxication also caused a decrease in GSH concentration, especially in the cerebellum, striatum, and cortex. This may be explained by the increase in the concentration of acetaldehyde, which is removed from cells with the use of this antioxidant. The antioxidative abilities of the CNS also depend on exogenous antioxidants which are provided to the organism during food intake. The most important exogenous antioxidant in the CNS is vitamin E. The content of vitamin E as well as that of vitamin C in the CNS is decreased, whereas the content of vitamin A is increased after ethanol administration. The high vitamin A level may cause damage of the central nervous system, especially in young rats exposed to ethanol in the prenatal period.