title: Creatine and pyruvate prevent behavioral and oxidative stress alterations caused by hypertryptophanemia in rats.
abstract: It is known that the accumulation of tryptophan and its metabolites is related to brain damage associated with both hypertryptophanemia and neurodegenerative diseases. In this study, we investigated the effect of tryptophan administration on various parameters of behavior in the open-field task and oxidative stress, and the effects of creatine and pyruvate, on the effect of tryptophan. Forty, 60-day-old male Wistar rats, were randomly divided into four groups: saline, tryptophan, pyruvate + creatine, tryptophan + pyruvate + creatine. Animals received three subcutaneous injections of tryptophan (2 μmol/g body weight each one at 3 h of intervals) and/or pyruvate (200 μg/g body weight 1 h before tryptophan), and/or creatine (400 μg/g body weight twice a day for 5 days before tryptophan twice a day for 5 days before training); controls received saline solution (NaCl 0.85%) at the same volumes (30 μl/g body weight) than the other substances. Results showed that tryptophan increased the activity of the animals, suggesting a reduction in the ability of habituation to the environment. Tryptophan induced increase of TBA-RS and total sulfhydryls. The effects of tryptophan in the open field, and in oxidative stress were fully prevented by the combination of creatine plus pyruvate. In case these findings also occur in humans affected by hypertryptophanemia or other neurodegenerative disease in which tryptophan accumulates, it is feasible that oxidative stress may be involved in the mechanisms leading to the brain injury, suggesting that creatine and pyruvate supplementation could benefit patients affected by these disorders.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Vivian Strassburger
authors.initials: VS
authors.lastname: Andrade
authors.forename: Denise Bertin
authors.initials: DB
authors.lastname: Rojas
authors.forename: Lenise
authors.initials: L
authors.lastname: Oliveira
authors.forename: Mychely Lopes
authors.initials: ML
authors.lastname: Nunes
authors.forename: Fernanda Luz
authors.initials: FL
authors.lastname: de Castro
authors.forename: Cristina
authors.initials: C
authors.lastname: Garcia
authors.forename: Tanise
authors.initials: T
authors.lastname: Gemelli
authors.forename: Rodrigo Binkowski
authors.initials: RB
authors.lastname: de Andrade
authors.forename: Clóvis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003401:Creatine / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D019289:Pyruvic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014364:Tryptophan / Q000494:pharmacology*
chemical_list: D019289:Pyruvic Acid; D014364:Tryptophan; D003401:Creatine
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