Pristanic acid promotes oxidative stress in brain cortex of young rats: a possible pathophysiological mechanism for brain damage in peroxisomal disorders.
Pristanic acid (Prist) is accumulated in various peroxisomal disorders characterized by severe neurological dysfunction whose pathogenesis is poorly understood. Since oxidative damage has been demonstrated in brain of patients affected by neurodegenerative disorders, in the present work we investigated the in vitro effects of Prist on important parameters of oxidative stress in cerebral cortex from young rats. Prist significantly increased malondialdehyde levels, reflecting an increase of lipid peroxidation. This effect was totally prevented by the free radical scavenger melatonin, suggesting the involvement of reactive species. Prist also provoked protein oxidative damage, as determined by increased carbonyl formation and sulfhydryl oxidation. Otherwise, it did not alter nitric oxide production, indicating that nitrogen reactive species were not implicated in the lipid and oxidative damage provoked by Prist. Furthermore, the concentration of glutathione (GSH), the major brain non-enzymatic antioxidant defense, was significantly decreased by Prist and this decrease was fully prevented by melatonin and attenuated by α-tocopherol. It is therefore presumed that Prist elicits oxidative stress in the brain probably via reactive oxygen species formation and that this pathomechanism may possibly be involved in the brain damage found in patients affected by peroxisomal disorders where Prist accumulates.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Rio Grande do Sul, Porto Alegre, RS, Brazil.
Guilhian
G
Leipnitz
Alexandre Umpierrez
AU
Amaral
Carolina Gonçalves
CG
Fernandes
Bianca
B
Seminotti
Angela
A
Zanatta
Lisiane Aurélio
LA
Knebel
Carmen Regla
CR
Vargas
Moacir
M
Wajner
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D001925:Brain Damage, Chronic / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D018901:Peroxisomal Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D005227:Fatty Acids; C002844:pristanic acid