Tryptophan administration induces oxidative stress in brain cortex of rats.
Despite the significant brain abnormalities, the neurotoxic mechanisms of brain injury in hypertryptophanemia are virtually unknown. In this work, we determined the thiobarbituric acid-reactive substances, 2',7'-dihydrodichlorofluorescein oxidation, reduced glutathione and the activities of catalase, superoxide dismutase and glutathione peroxidase in cerebral cortex from rats loaded with L-tryptophan. High L-tryptophan concentrations, similar to those found in hypertryptophanemic patients were induced by three subcutaneous injections of saline-buffered tryptophan (2 micromol/g body weight) to 30-day-old Wistar rats. The parameters were assessed 1 h after the last injection. It was observed that tryptophan significantly increased thiobarbituric acid-reactive substances, 2',7'-dihydrodichlorofluorescein oxidation and reduced glutathione, whereas it reduced catalase activity. Pre-treatment with taurine (1.6 micromol/g of body weight), or alpha-tocopherol plus ascorbic acid (40 and 100 microg/g body weight, respectively) prevented those effects of tryptophan, reinforcing the hypothesis that tryptophan induces oxidative stress in brain cortex of the rats. Therefore, these findings also occur in human hypertryptophanemia or in other neurodegenerative diseases in which tryptophan accumulates, then oxidative stress may be involved in the mechanisms leading to the brain injury observed in patients affected by these disorders.
Feksa
Luciane Rosa
LR
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. lucianef@feevale.br
Latini
Alexandra
A
Rech
Virgínia Cielo
VC
Feksa
Patrícia Bartels
PB
Koch
Gustavo Duarte Waltereith
GD
Amaral
Maria Fernanda Arevalo
MF
Leipnitz
Guilhian
G
Dutra-Filho
Carlos Severo
CS
Wajner
Moacir
M
Wannmacher
Clóvis Milton Duval
CM
D000592:Amino Acid Metabolism, Inborn Errors / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001928:Brain Diseases, Metabolic / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013654:Taurine / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism* / Q000633:toxicity; D024502:alpha-Tocopherol / Q000494:pharmacology
D000975:Antioxidants; C000606290:SOD1 protein, human; D017392:Thiobarbituric Acid Reactive Substances; D013654:Taurine; D014364:Tryptophan; D002374:Catalase; D005979:Glutathione Peroxidase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione; D024502:alpha-Tocopherol