title: Pipecolic acid induces oxidative stress in vitro in cerebral cortex of young rats and the protective role of lipoic acid.
abstract: Pipecolic acid (PA) levels are increased in severe metabolic disorders of the central nervous system such as Zellweger syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and hyperlysinemia. The affected individuals present progressive neurological dysfunction, hypotonia and growth retardation. The mechanisms of brain damage of these disorders remain poorly understood. Since PA catabolism can produce H2O2 by oxidases, oxidative stress may be a possible mechanism involved in the pathophysiology of these diseases. Lipoic acid (LA) is considered an efficient antioxidant and has been shown to prevent oxidative stress in experimental models of many disorders of the neurologic system. Considering that to our knowledge no study investigated the role of PA on oxidative stress, in the present work we investigated the in vitro effects of PA on some oxidative stress parameters and evaluated the LA efficacy against possible pro-oxidant effects of PA in cerebral cortex of 14-day-old rats. The activities of catalase (CAT), glutathione peroxidase (GPx), glucose 6-phosphate dehydrogenase (G6PD), and glutathione S-transferase (GST) along with reduced glutathione (GSH) content were significantly decreased, while superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBA-RS) were significantly enhanced by PA. LA was able to prevent these effects by improving the activity of antioxidant enzymes, increasing GSH content and reducing TBA-RS. In contrast, glutathione reductase and 6-phosphogluconate dehydrogenase activities and sulfhydryl content were not affected. Taken together, it may be presumed that PA in vitro elicits oxidative stress and LA is able to prevent these effects.
authors: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors: Giovana Reche
authors: GR
authors: Dalazen
authors: Melaine
authors: M
authors: Terra
authors: Carlos Eduardo Diaz
authors: CE
authors: Jacques
authors: Juliana G
authors: JG
authors: Coelho
authors: Raylane
authors: R
authors: Freitas
authors: Priscila Nicolao
authors: PN
authors: Mazzola
authors: Carlos Severo
authors: CS
authors: Dutra-Filho
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000032:analysis; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D005978:Glutathione / Q000032:analysis; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008239:Lysine / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000032:analysis; D010875:Pipecolic Acids / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000032:analysis; D013482:Superoxide Dismutase / Q000032:analysis; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010875:Pipecolic Acids; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D008063:Thioctic Acid; D010088:Oxidoreductases; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; C031345:pipecolic acid; D008239:Lysine