title: L-tyrosine induces DNA damage in brain and blood of rats.
abstract: Mutations in the tyrosine aminotransferase gene have been identified to cause tyrosinemia type II which is inherited in an autosomal recessive manner. Studies have demonstrated that an excessive production of ROS can lead to reactions with macromolecules, such as DNA, lipids, and proteins. Considering that the L-tyrosine may promote oxidative stress, the main objective of this study was to investigate the in vivo effects of L-tyrosine on DNA damage determined by the alkaline comet assay, in brain and blood of rats. In our acute protocol, Wistar rats (30 days old) were killed 1 h after a single intraperitoneal L-tyrosine injection (500 mg/kg) or saline. For chronic administration, the animals received two subcutaneous injections of L-tyrosine (500 mg/kg, 12-h intervals) or saline administered for 24 days starting at postnatal day (PD) 7 (last injection at PD 31), 12 h after the last injection, the animals were killed by decapitation. We observed that acute administration of L-tyrosine increased DNA damage frequency and damage index in cerebral cortex and blood when compared to control group. Moreover, we observed that chronic administration of L-tyrosine increased DNA damage frequency and damage index in hippocampus, striatum, cerebral cortex and blood when compared to control group. In conclusion, the present work demonstrated that DNA damage can be encountered in brain from animal models of hypertyrosinemia, DNA alterations may represent a further means to explain neurological dysfunction in this inherited metabolic disorder and to reinforce the role of oxidative stress in the pathophysiology of tyrosinemia type II.
authors.affiliation: Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil.
authors.forename: Samira D T
authors.initials: SD
authors.lastname: De Prá
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Ferreira
authors.forename: Milena
authors.initials: M
authors.lastname: Carvalho-Silva
authors.forename: Júlia S
authors.initials: JS
authors.lastname: Vieira
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Leffa
authors.forename: Gabriela E
authors.initials: GE
authors.lastname: Fagundes
authors.forename: Bruno N
authors.initials: BN
authors.lastname: Bristot
authors.forename: Gabriela D
authors.initials: GD
authors.lastname: Borges
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Ferreira
authors.forename: Patrícia F
authors.initials: PF
authors.lastname: Schuck
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Andrade
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000633:toxicity*; D014444:Tyrosine Transaminase / Q000235:genetics; D020176:Tyrosinemias / Q000139:chemically induced
chemical_list: D014443:Tyrosine; D014444:Tyrosine Transaminase