title: Tryptophan administration induces oxidative stress in brain cortex of rats.
abstract: 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.
authors.affiliation: 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
authors.forename: Luciane Rosa
authors.initials: LR
authors.lastname: Feksa
authors.forename: Alexandra
authors.initials: A
authors.lastname: Latini
authors.forename: Virgínia Cielo
authors.initials: VC
authors.lastname: Rech
authors.forename: Patrícia Bartels
authors.initials: PB
authors.lastname: Feksa
authors.forename: Gustavo Duarte Waltereith
authors.initials: GD
authors.lastname: Koch
authors.forename: Maria Fernanda Arevalo
authors.initials: MF
authors.lastname: Amaral
authors.forename: Guilhian
authors.initials: G
authors.lastname: Leipnitz
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Clóvis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
mesh_terms: 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
chemical_list: 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