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: Luciane Rosa Feksa, Alexandra Latini, Virgínia Cielo Rech, Patrícia Bartels Feksa, Gustavo Duarte Waltereith Koch, Maria Fernanda Arevalo Amaral, Guilhian Leipnitz, Carlos Severo Dutra-Filho, Moacir Wajner, Clóvis Milton Duval Wannmacher
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 23 Issue 2 Pg. 221-33 (Jun 2008) ISSN: 0885-7490 [Print] United States
• PMID: 18425567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• SOD1 protein, human
• Thiobarbituric Acid Reactive Substances
• Taurine
• Tryptophan
• Catalase
• Glutathione Peroxidase
• Sod1 protein, rat
• Superoxide Dismutase
• Superoxide Dismutase-1
• Glutathione
• alpha-Tocopherol

Topics

• Amino Acid Metabolism, Inborn Errors (chemically induced, metabolism, physiopathology)
• Animals
• Antioxidants (pharmacology)
• Brain Diseases, Metabolic (chemically induced, metabolism, physiopathology)
• Catalase (metabolism)
• Cell Death (drug effects, physiology)
• Cerebral Cortex (drug effects, metabolism, physiopathology)
• Disease Models, Animal
• Glutathione (metabolism)
• Glutathione Peroxidase (metabolism)
• Male
• Nerve Degeneration (chemically induced, metabolism, physiopathology)
• Neurons (drug effects, metabolism)
• Oxidative Stress (drug effects, physiology)
• Rats
• Rats, Wistar
• Superoxide Dismutase (metabolism)
• Superoxide Dismutase-1
• Taurine (pharmacology)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Tryptophan (metabolism, toxicity)
• alpha-Tocopherol (pharmacology)