Promotion of lipid and protein oxidative damage in rat brain by ethylmalonic acid.
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.
Schuck
Patrícia Fernanda
PF
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.
Busanello
Estela Natacha Brandt
EN
Moura
Alana Pimentel
AP
Tonin
Anelise Miotti
AM
Grings
Mateus
M
Ritter
Luciana
L
Vargas
Carmen Regla
CR
da Costa Ferreira
Gustavo
G
Wajner
Moacir
M
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
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