title: Neurotoxic effects of trans-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 the in vitro effect of increasing tGA concentrations on neurochemical and oxidative stress parameters in rat cerebral cortex. We observed that Na(+), K(+)-ATPase activity was reduced by tGA, 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 that tGA may be neurotoxic in rat brain.
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Patrícia F
authors.initials: PF
authors.lastname: Schuck
authors.forename: Estela N B
authors.initials: EN
authors.lastname: Busanello
authors.forename: Anelise M
authors.initials: AM
authors.lastname: Tonin
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Viegas
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Ferreira
mesh_terms: D025181:ATP Synthetase Complexes / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D005977:Glutarates / Q000633:toxicity*; D007536:Isomerism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D005977:Glutarates; D011506:Proteins; D013438:Sulfhydryl Compounds; C010971:glutaconic acid; D003402:Creatine Kinase; D025181:ATP Synthetase Complexes; D000254:Sodium-Potassium-Exchanging ATPase