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

• Published in: Molecular neurobiology 2018-06, Vol.55 (6), p.5101-5110
• Main Authors: Gemelli, Tanise, de Andrade, Rodrigo Binkowski, Rojas, Denise Bertin, Zanatta, Ângela, Schirmbeck, Gabriel Henrique, Funchal, Cláudia, Wajner, Moacir, Dutra-Filho, Carlos Severo, Wannmacher, Clovis Milton Duval
• Format: Article
• Language: English
• Subjects: Alanine; Amino acids; Animals; Antioxidants; beta-Alanine - administration & dosage; beta-Alanine - toxicity; Biomedical and Life Sciences; Biomedicine; Body weight; Cell Biology; Central nervous system; Cerebellum; Cerebellum - pathology; Cerebral cortex; Cerebral Cortex - pathology; Chronic exposure; Creatine; Creatine kinase; Dehydrogenase; Dehydrogenases; Electron Transport Chain Complex Proteins - metabolism; Energy metabolism; Energy Metabolism - drug effects; Enzymes; Glutathione peroxidase; Glyceraldehyde; Glyceraldehyde 3-phosphate; Glyceraldehyde-3-phosphate dehydrogenase; Hexokinase; Inborn errors of metabolism; Metabolism; Neurobiology; Neurology; Neuromodulation; Neurosciences; Oxidative stress; Oxidative Stress - drug effects; Peritoneum; Rats; Rats, Wistar; Reactive oxygen species; Rodents; Sodium chloride; Superoxide dismutase; Tissues; γ-Aminobutyric acid
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-017-0711-3

β-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 γ-aminobutyric acid (GABA). The β-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 β-alaninemia. We evaluated the effects of the chronic administration of β-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 β-alanine (300 mg/kg of body weight), and the controls received the same volume (10 μl/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 β-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 β-alanine administration increased the activities of complex II, complex IV and succinate dehydrogenase (SDH). Those results suggest that the chronic administration of β-alanine causes cellular oxidative damage, significantly changing the energy metabolism.