Does ascorbate/l-cys/l-met mixture protect different parts of the rat brain against chronic alcohol toxicity?

Abstract

Chronic ingestion of high levels of alcohol may cause oxidative stress that results in the formation, through alcohol metabolism, of excess free radicals, acetaldehyde, lipid and protein oxidation, and their reactivity products. These harmful molecules may trigger oxidative damage to neurons and can cause cell death. It is hypothesized that cysteine-methionine and vitamin C may neutralize these harmful compounds while potentiating the antioxidant capacity of the cell or tissue. In the present study, rats were fed regular diets and were maintained for 90 days in (1) the control group, (2) the alcoholic group, which was given 2.5 g of 50% ethanol/kg body weight administered intragastrically every other day, or (3) the alcoholic with antioxidant supplement group, to whom 2.5 g of 50% ethanol/kg body weight + a solution that contained 200 mg vitamin C, 100 mg cysteine, and 100 mg methionine was administered intragastrically every other day. The mean blood alcohol level was raised by 40% in the alcoholic group compared with the control group, but, compared with the alcoholic group, the alcohol level was decreased by 30% in the antioxidant-supplemented group. In keeping with blood alcohol levels, oxidized protein and lipid content in the cerebrum, brain stem, and cerebellum were low in the control group, higher in the antioxidant-supplemented group, and highest in the alcoholic group. The mean total thiol level was higher in the antioxidant-supplemented group than in the alcoholic and control groups. It is interesting to note that the level of total glutathione in the cerebrum and cerebellum in the alcoholic group was lower than in the control and antioxidant-supplemented groups. In conclusion, long-term alcohol administration led to increased levels of oxidized protein and lipids in the cerebrum, brain stem, and cerebellum of rats. Simultaneous intake of ascorbate/ l-cys/l-met and ethanol attenuated the amount of oxidation that occurred, which suggested that cysteine, methionine, and vitamin C may play a protective role in the central nervous system against oxidative damage caused by alcohol consumption. In addition, the mean alcohol level was increased in the alcoholic group compared with the control group. The level of total glutathione was significantly decreased in the cerebellum of the alcoholic group, and oxidative damage was noted in various parts of the brain in this group. These findings suggest that oxidative stress plays a pathogenetic role in brain damage related to chronic alcoholism.