Chronic Exposure to beta-Alanine Generates Oxidative Stress and Alters Energy Metabolism in Cerebral Cortex and Cerebellum of Wistar Rats

beta-Alanine occurs naturally in the human central nervous system and performs different functions. It can act as either a neurotransmitter or a neuromodulator, depletion of taurine levels and competitive antagonist of gamma-aminobutyric acid (GABA). The beta-amino acid accumulation exerts an important biological function as delay in brain development, oxidative stress and disturbances in energy metabolism, characterized as an inborn error of metabolism classified as beta-alaninemia. We evaluated the effects of the chronic administration of beta-alanine on some parameters of oxidative stress and enzymes of energy metabolism in cerebral cortex and cerebellum of 21-day-old Wistar rats. The animals received peritoneal injections of beta-alanine (300 mg/kg of body weight), and the controls received the same volume (10 mu l/g of body weight) of saline solution (NaCl 0.9%), twice a day at 12-h interval, from the 7th to the 21st postpartum day. We observed that beta-amino acid was able to increase the levels of reactive oxygen species (ROS) in the two tissues; however, only in cerebral cortex total content of sulfhydryl was increased. ROS are possibly acting on antioxidant enzymes glutathione peroxidase (GPx) (cerebral cortex and cerebellum) and superoxide dismutase (SOD) (cerebellum) inhibiting their activities. We also evaluated the activities of enzymes of the phosphoryl transfer network, where we observed an increase in hexokinase and cytosolic creatine kinase (Cy-CK) activities; however, it decreased glyceraldehyde 3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) activities, in both tissues. Besides, the beta-alanine administration increased the activities of complex II, complex IV and succinate dehydrogenase (SDH). Those results suggest that the chronic administration of beta-alanine causes cellular oxidative damage, significantly changing the energy metabolism.