Tyrosine administration decreases glutathione and stimulates lipid and protein oxidation in rat cerebral cortex

Metab Brain Dis. 2009 Sep;24(3):415-25. doi: 10.1007/s11011-009-9153-6. Epub 2009 Aug 18.

Abstract

Tyrosine levels are abnormally elevated in tissues and physiological fluids of patients with inborn errors of tyrosine catabolism especially in tyrosinemia type II which is caused by deficiency of tyrosine aminotransferase (TAT) and provokes eyes, skin and central nervous system disturbances. We have recently reported that tyrosine promoted oxidative stress in vitro but the exact mechanisms of brain damage in these disorder are poorly known. In the present study, we investigated the in vivo effect of L-tyrosine (500 mg/Kg) on oxidative stress indices in cerebral cortex homogenates of 14-day-old Wistar rats. A single injection of L-tyrosine decreased glutathione (GSH) and thiol-disulfide redox state (SH/SS ratio) while thiobarbituric acid-reactive substances, protein carbonyl content and glucose-6-phosphate dehydrogenase activity were enhanced. In contrast, the treatment did not affect ascorbic acid content, and the activities of superoxide dismutase, catalase and glutathione peroxidase. These results indicate that acute administration of L-tyrosine may impair antioxidant defenses and stimulate oxidative damage to lipids and proteins in cerebral cortex of young rats in vivo. This suggests that oxidative stress may represent a pathophysiological mechanism in hypetyrosinemic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / metabolism
  • Catalase / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Disulfides / metabolism
  • Glucosephosphate Dehydrogenase / metabolism
  • Glutathione / metabolism*
  • Glutathione Peroxidase / metabolism
  • Lipid Metabolism / drug effects*
  • Lipid Peroxidation / drug effects
  • Nerve Tissue Proteins / metabolism*
  • Oxidation-Reduction
  • Protein Carbonylation / drug effects
  • Rats
  • Rats, Wistar
  • Stimulation, Chemical
  • Sulfhydryl Compounds / metabolism
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Tyrosine / pharmacology*

Substances

  • Disulfides
  • Nerve Tissue Proteins
  • Sulfhydryl Compounds
  • Thiobarbituric Acid Reactive Substances
  • Tyrosine
  • Glucosephosphate Dehydrogenase
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione
  • Ascorbic Acid