title: L-Carnitine supplementation decreases DNA damage in treated MSUD patients.
abstract: Maple syrup urine disease (MSUD) is an inherited disorder caused by severe deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their α-ketoacid derivatives. MSUD patients generally present ketoacidosis, poor feeding, ataxia, coma, psychomotor delay, mental retardation and brain abnormalites. Treatment consists of dietary restriction of the BCAA (low protein intake) supplemented by a BCAA-free amino acid mixture. Although the mechanisms of brain damage in MSUD are poorly known, previous studies have shown that oxidative stress may be involved in the neuropathology of this disorder. In this regard, it was recently reported that MSUD patients have deficiency of l-carnitine (l-car), a compound with antioxidant properties that is used as adjuvant therapy in various inborn errors of metabolism. In this work, we investigated DNA damage determined by the alkaline comet assay in peripheral whole blood leukocytes of MSUD patients submitted to a BCAA-restricted diet supplemented or not with l-car. We observed a significant increase of DNA damage index (DI) in leukocytes from MSUD patients under BCAA-restricted diet as compared to controls and that l-car supplementation significantly decreased DNA DI levels. It was also found a positive correlation between DI and MDA content, a marker of lipid peroxidation, and an inverse correlation between DI and l-car levels. Taken together, our present results suggest a role for reactive species and the involvement of oxidative stress in DNA damage in this disorder. Since l-car reduced DNA damage, it is presumed that dietary supplementation of this compound may serve as an adjuvant therapeutic strategy for MSUD patients in addition to other therapies.
authors: Programa de Pós-Graduação em CB:Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035 000, Porto Alegre, RS, Brazil. Electronic address: carolmescka@yahoo.com.br.
authors: Caroline Paula
authors: CP
authors: Mescka
authors: Faculdade de Farmácia, UFRGS, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
authors: Gilian
authors: G
authors: Guerreiro
authors: Faculdade de Farmácia, UFRGS, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
authors: Tatiane
authors: T
authors: Hammerschmidt
authors: Faculdade de Farmácia, UFRGS, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
authors: Jéssica
authors: J
authors: Faverzani
authors: Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil.
authors: Daniella
authors: D
authors: de Moura Coelho
authors: Universidade Federal do Pampa, BR 472, Km 585, Caixa Postal 118, 97500 970 Uruguaiana, RS, Brazil.
authors: Vanusa
authors: V
authors: Mandredini
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, 90610-000 Porto Alegre, RS, Brazil.
authors: Carlos Alberto Yasin
authors: CA
authors: Wayhs
authors: Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em CB:Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035 000, Porto Alegre, RS, Brazil.
authors: Moacir
authors: M
authors: Wajner
authors: Programa de Pós-Graduação em CB:Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035 000, Porto Alegre, RS, Brazil.
authors: Carlos Severo
authors: CS
authors: Dutra-Filho
authors: Faculdade de Farmácia, UFRGS, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil; Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em CB:Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035 000, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, 90610-000 Porto Alegre, RS, Brazil.
authors: Carmen Regla
authors: CR
authors: Vargas
mesh_terms: D002331:Carnitine / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D004249:DNA Damage; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008375:Maple Syrup Urine Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D014803:Vitamin B Complex / Q000008:administration & dosage*
chemical_list: D014803:Vitamin B Complex; D002331:Carnitine
keywords: Antioxidant; DNA damage; Maple syrup urine disease; Oxidative stress; l-Carnitine