Neurotoxic Effects oftrans-Glutaconic Acid in Rats

Abstract

trans-Glutaconic acid (tGA) 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 thein vitroeffect of increasingtGA concentrations on neurochemical and oxidative stress parameters in rat cerebral cortex. We observed that Na+, K+-ATPase activity was reduced bytGA, but not creatine kinase, respiratory chain complex IV, and ATP synthase activities. On the other hand,tGA significantly increased lipid peroxidation (thiobarbituric acid-reactive species levels and spontaneous chemiluminescence), as well as protein oxidative damage (oxidation of sulfhydryl groups).tGA also significantly decreased nonenzymatic antioxidant defenses (TRAP and reduced glutathione levels). Our data suggest thattGA may be neurotoxic in rat brain.