title: The characterization of neuroenergetic effects of chronic L-tyrosine administration in young rats: evidence for striatal susceptibility.
abstract: Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in hepatic cytosolic aminotransferase. Affected patients usually present a variable degree of mental retardation, which may be related to the level of plasma tyrosine. In the present study we evaluated effect of chronic administration of L-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase and complexes I, II, II-III and IV in cerebral cortex, hippocampus and striatum of rats in development. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old); rats were killed 12 h after last injection. Our results demonstrated that L-tyrosine inhibited the activity of citrate synthase in the hippocampus and striatum, malate dehydrogenase activity was increased in striatum and succinate dehydrogenase, complexes I and II-III activities were inhibited in striatum. However, complex IV activity was increased in hippocampus and inhibited in striatum. By these findings, we suggest that repeated administrations of L-tyrosine cause alterations in energy metabolism, which may be similar to the acute administration in brain of infant rats. Taking together the present findings and evidence from the literature, we hypothesize that energy metabolism impairment could be considered an important pathophysiological mechanism underlying the brain damage observed in patients with tyrosinemia type II.
authors.affiliation: Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Ferreira
authors.forename: Milena
authors.initials: M
authors.lastname: Carvalho-Silva
authors.forename: Lara M
authors.initials: LM
authors.lastname: Gomes
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.forename: Leticia J
authors.initials: LJ
authors.lastname: Teixeira
authors.forename: Isabella T
authors.initials: IT
authors.lastname: Mota
authors.forename: Patrícia F
authors.initials: PF
authors.lastname: Schuck
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Ferreira
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D002950:Citrate (si)-Synthase / Q000032:analysis / Q000037:antagonists & inhibitors; D002952:Citric Acid Cycle / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D045222:Electron Transport Chain Complex Proteins / Q000032:analysis / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008291:Malate Dehydrogenase / Q000032:analysis / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000633:toxicity*; D020176:Tyrosinemias
chemical_list: D045222:Electron Transport Chain Complex Proteins; D009419:Nerve Tissue Proteins; D014443:Tyrosine; D008291:Malate Dehydrogenase; D002950:Citrate (si)-Synthase