title: Promotion of lipid and protein oxidative damage in rat brain by ethylmalonic acid.
abstract: High concentrations of ethylmalonic acid are found in tissues and biological fluids of patients affected by ethylmalonic encephalopathy, deficiency of short-chain acyl-CoA dehydrogenase activity and other illnesses characterized by developmental delay and neuromuscular symptoms. The pathophysiological mechanisms responsible for the brain damage in these patients are virtually unknown. Therefore, in the present work we investigated the in vitro effect of EMA on oxidative stress parameters in rat cerebral cortex. EMA significantly increased chemiluminescence and thiobarbituric acid-reactive species levels (lipoperoxidation), as well as carbonyl content and oxidation of sulfhydryl groups (protein oxidative damage) and DCFH. EMA also significantly decreased the levels of reduced glutathione (non-enzymatic antioxidant defenses). In contrast, nitrate and nitrite levels were not affected by this short organic acid. It is therefore presumed that oxidative stress may represent a pathomechanism involved in the pathophysiology of the neurologic symptoms manifested by patients affected by disorders in which EMA accumulates.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Patrícia Fernanda
authors.initials: PF
authors.lastname: Schuck
authors.forename: Estela Natacha Brandt
authors.initials: EN
authors.lastname: Busanello
authors.forename: Alana Pimentel
authors.initials: AP
authors.lastname: Moura
authors.forename: Anelise Miotti
authors.initials: AM
authors.lastname: Tonin
authors.forename: Mateus
authors.initials: M
authors.lastname: Grings
authors.forename: Luciana
authors.initials: L
authors.lastname: Ritter
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
authors.forename: Gustavo
authors.initials: G
authors.lastname: da Costa Ferreira
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D044926:Butyryl-CoA Dehydrogenase / Q000172:deficiency; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D005452:Fluoresceins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008314:Malonates / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002839:Chromans; D005452:Fluoresceins; D008314:Malonates; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; C065013:2',7'-dichlorodihydrofluorescein; C038080:ethylmalonic acid; D044926:Butyryl-CoA Dehydrogenase; D005978:Glutathione; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid