title: L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD.
abstract: Maple syrup urine disease (MSUD), or branched-chain α-keto aciduria, is an inherited disorder that is caused by a deficiency in branched-chain α-keto acid dehydrogenase complex (BCKAD) activity. Blockade of this pathway leads to the accumulation of the branched-chain amino acids (BCAAs), leucine, isoleucine, and valine, and their respective ketoacids in tissues. The main clinical symptoms presented by MSUD patients include ketoacidosis, hypoglycemia, opisthotonos, poor feeding, apnea, ataxia, convulsions, coma, psychomotor delay, and mental retardation. Although increasing evidence indicates that oxidative stress is involved in the pathophysiology of this disease, the mechanisms of the brain damage caused by this disorder remain poorly understood. In the present study, we investigated the effect of BCAAs on some oxidative stress parameters and evaluated the efficacy of L-carnitine (L-car), an efficient antioxidant that may be involved in the reduction of oxidative damage observed in some inherited neurometabolic diseases, against these possible pro-oxidant effects of a chronic MSUD model in the cerebral cortex and cerebellum of rats. Our results showed that chronic BCAA administration was able to promote both lipid and protein oxidation, impair brain antioxidant defenses, and increase reactive species production, particularly in the cerebral cortex, and that L-car was able to prevent these effects. Taken together, the present data indicate that chronic BCAA administration significantly increased oxidative damage in the brains of rats subjected to a chronic model of MSUD and that L-car may be an efficient antioxidant in this disorder.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035-000, Porto Alegre, Rio Grande do Sul, Brazil.|Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Caroline Paula
authors.initials: CP
authors.lastname: Mescka
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035-000, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Andrea Pereira
authors.initials: AP
authors.lastname: Rosa
authors.affiliation: Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, 90035-000, Rio Grande do Sul, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Schirmbeck
authors.affiliation: Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, 90035-000, Rio Grande do Sul, Brazil.
authors.forename: Thales Hein
authors.initials: TH
authors.lastname: da Rosa
authors.affiliation: Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, 90035-000, Rio Grande do Sul, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Catarino
authors.affiliation: Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, 90035-000, Rio Grande do Sul, Brazil.
authors.forename: Laila Oliveira
authors.initials: LO
authors.lastname: de Souza
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, Porto Alegre, 90610-000, Rio Grande do Sul, Brazil.|Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Gilian
authors.initials: G
authors.lastname: Guerreiro
authors.affiliation: Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Angela
authors.initials: A
authors.lastname: Sitta
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035-000, Porto Alegre, Rio Grande do Sul, Brazil.|Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, Porto Alegre, 90610-000, Rio Grande do Sul, Brazil.|Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
authors.affiliation: Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, 90035-000, Rio Grande do Sul, Brazil. dutra@ufrgs.br.|Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035-000, Porto Alegre, Rio Grande do Sul, Brazil. dutra@ufrgs.br.
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000473:pathology*; D002331:Carnitine / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D008375:Maple Syrup Urine Disease / Q000139:chemically induced* / Q000473:pathology*; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D002331:Carnitine
keywords: Antioxidant; Branched-chain amino acids; L-carnitine; Maple syrup urine disease; Neuroprotection; Oxidative stress