Promotion of oxidative stress by L-tryptophan in cerebral cortex of rats.
Despite the significant brain abnormalities, the neurotoxic mechanisms of brain injury in hypertryptophanemia are virtually unknown. In this work, it was investigated the in vitro effect of l-tryptophan on various parameters of oxidative stress, namely spontaneous chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR) and glutathione (GSH) levels in cerebral cortex from 30-day-old rats. Tryptophan significantly increased chemiluminescence and TBA-RS measurements indicating that this amino acid induced lipid peroxidation in vitro. We also observed that tryptophan significantly decreased the brain antioxidant defenses by reducing the values of TRAP, TAR and GSH, reflecting that the overall content of antioxidants was reduced by tryptophan. Furthermore, the tryptophan-induced increase of TBA-RS was fully prevented by GSH and by combination of catalase plus superoxide dismutase, but not by the inhibitor of nitric oxide synthase N(omega)-nitro-L-arginine methyl ester (L-NAME). In case these findings also occur in human hypertryptophanemia or in other neurodegenerative diseases in which tryptophan accumulates, it is feasible that oxidative stress may be involved in the mechanism leading to the brain injury observed in patients affected by these disorders.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Luciane Rosa
LR
Feksa
Alexandra
A
Latini
Virgínia Cielo
VC
Rech
Moacir
M
Wajner
Carlos Severo
CS
Dutra-Filho
Angela Terezinha
AT
de Souza Wyse
Clovis Milton Duval
CM
Wannmacher
D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D049449:Luminescence; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism* / Q000633:toxicity
D000975:Antioxidants; D004791:Enzyme Inhibitors; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D014364:Tryptophan; D002374:Catalase; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester