Neurotoxic Effects oftrans-Glutaconic Acid in Rats

trans -Glutaconic acid ( t GA) is an unsaturated C5-dicarboxylic acid which may be found accumulated in glutaric aciduria type I, whose pathophysiology is still uncertain. In the present work it was investigated the in vitro effect of increasing t GA concentrations on neurochemical and oxidative stress parameters in rat cerebral cortex. We observed that Na + , K + -ATPase activity was reduced by t GA, but not creatine kinase, respiratory chain complex IV, and ATP synthase activities. On the other hand, t GA significantly increased lipid peroxidation (thiobarbituric acid-reactive species levels and spontaneous chemiluminescence), as well as protein oxidative damage (oxidation of sulfhydryl groups). t GA also significantly decreased nonenzymatic antioxidant defenses (TRAP and reduced glutathione levels). Our data suggest that t GA may be neurotoxic in rat brain.