Protein oxidative damage in arsenic induced rat brain:: influence of DL-α-lipoic acid

A body of evidence has accumulated implicating free radical generation and reaction of arsenic with protein thiols in the biochemical and molecular mechanisms of arsenic toxicity. Brain readily undergoes oxidative damage, so it is important to determine whether arsenic-induced changes in rat brain may be associated with oxidative events. An increase in oxidative stress may contribute to the development of protein damage in rat brain. Present experiments were per-formed to study the effect of arsenic (sodium arsenite, 100ppm mixed in drinking water) on protein oxidation and further to demonstrate the potential Of DL-alpha-lipoic acid (70mg/kg body weight) against arsenic-induced changes in different anatomic regions (cortex, striatum, cerebellum, hypothalamus and hippocampus) of the brain of male Wistar rats. We report here that arsenic treated rats had a significantly higher level of oxidised protein as assessed by increased carbonyl residues and decreased protein thiols (protein sulfhydryls) as compared to control rats in all five regions studied, with the most notable changes occurring in the cortex, striatum and hippocampus. Coadministration of lipoic acid along with arsenic resulted in reversal of the arsenic induced trends in carbonyl and sulfhydryl concentrations. The results of the study showed, lipoic acid treatment reduces oxidative protein damage in arsenic intoxicated rat brain regions, which is associated with its antioxidant activity that combines free radical scavenging and metal chelating properties. (C) 2004 Elsevier Ireland Ltd. All rights reserved.