Metab Brain Dis (2009) 24:415–425 DOI 10.1007/s11011-009-9153-6 O R I G I N A L PA P E R
Tyrosine administration decreases glutathione and stimulates lipid and protein oxidation in rat cerebral cortex Ângela M. Sgaravatti & Alessandra S. Magnusson & Amanda S. de Oliveira & Andréa P. Rosa & Caroline Paula Mescka & Fernanda R. Zanin & Carolina D. Pederzolli & Angela T. S. Wyse & Clóvis M. D. Wannmacher & Moacir Wajner & Carlos Severo Dutra-Filho
Received: 26 February 2009 / Accepted: 28 April 2009 / Published online: 18 August 2009 # Springer Science + Business Media, LLC 2009
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 A. S. Magnusson : A. S. de Oliveira : A. P. Rosa : C. P. Mescka : F. R. Zanin : A. T. S. Wyse : C. M. D. Wannmacher : M. Wajner : C. S. Dutra-Filho Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600–Anexo, CEP 90035-003 Porto Alegre, RS, Brazil Â. M. Sgaravatti : C. D. Pederzolli : A. T. S. Wyse : C. M. D. Wannmacher : M. Wajner : C. S. Dutra-Filho (*) Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil e-mail:
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Metab Brain Dis (2009) 24:415–425
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. Keywords Tyrosine . Hypertyrosinemias . Tyrosinemia type II . Tyrosine administration . Rat brain . Oxidative stress
Introduction Inherited deficiencies of enzymes involved in tyrosine catabolism leads to hypertyrosinemia. Three distinct autosomal recessive diseases of tyrosine metabolism have been identified in humans: tyrosinemia type I (deficiency of fumarylacetoacetate hydrolase (FAH)), tyrosinemia type II (deficiency of tyrosine aminotransferase (TAT)), and tyrosinemia type III (deficiency of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD)) (Mitchell et al. 2001; Russo et al. 2001; Held 2006). Hypertyrosinemia is associated with neurologic and development difficulties in several patients with TAT deficiency and, less frequently, in patients with 4-HPPD deficiency and transient hypertyrosinemia (Light et al. 1973; Mamunes et al. 1976; Rice et al. 1989). Interestingly, plasma tyrosine levels are higher in TAT-deficiency comparing to the other causes of hypertyrosinemias and range from 370 to 3,420µM (normal
