Oxidative stress induction by cis-4-decenoic acid: relevance for MCAD deficiency.
Patients affected by medium-chain acyl-CoA dehydrogenase deficiency (MCADD) suffer from acute episodes of encephalopathy whose underlying mechanisms are poorly known. The present work investigated the in vitro effect of cis-4-decenoic acid (cDA), which accumulates in MCADD, on important parameters of oxidative stress in cerebral cortex of young rats. cDA markedly induced lipid peroxidation, as verified by the increased levels of spontaneous chemiluminescence and thiobarbituric acid-reactive substances. Furthermore, cDA significantly increased carbonyl formation and sulphydryl oxidation, which is indicative of protein oxidative damage, and promoted 2',7'-dihydrodichlorofluorescein oxidation. It was also observed that the non-enzymatic tissue antioxidant defenses were decreased by cDA, whereas the antioxidant enzyme activities catalase, superoxide dismutase and glutathione peroxidase were not altered. Moreover, cDA-induced lipid peroxidation and GSH reduction was totally blocked by free radical scavengers, suggesting that reactive species were involved in these effects. The data indicate that oxidative stress is induced by cDA in rat brain in vitro and that oxidative damage might be involved in the pathophysiology of the encephalopathy in MCADD.
Schuck
Patrícia F
PF
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Ceolato
Paula C
PC
Ferreira
Gustavo C
GC
Tonin
Anelise
A
Leipnitz
Guilhian
G
Dutra-Filho
Carlos S
CS
Latini
Alexandra
A
Wajner
Moacir
M
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D020739:Brain Diseases, Metabolic, Inborn / Q000209:etiology* / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005452:Fluoresceins / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D005229:Fatty Acids, Monounsaturated; D005452:Fluoresceins; D017392:Thiobarbituric Acid Reactive Substances; C065013:2',7'-dichlorodihydrofluorescein; D013481:Superoxides; C055444:4-decenoic acid; D042964:Acyl-CoA Dehydrogenase