title: Urinary biomarkers of oxidative damage in Maple syrup urine disease: the L-carnitine role.
abstract: Maple syrup urine disease (MSUD) is a disorder of branched-chain amino acids (BCAA). The defect in the branched-chain α-keto acid dehydrogenase complex activity leads to an accumulation of these compounds and their corresponding α-keto-acids and α-hydroxy-acids. Studies have shown that oxidative stress may be involved in neuropathology of MSUD. L-carnitine (L-car), which has demonstrated an important role as antioxidant by reducing and scavenging free radicals formation and by enhancing the activity of antioxidant enzymes, have been used in the treatment of some metabolic rare disorders. This study evaluated the oxidative stress parameters, di-tyrosine, isoprostanes and antioxidant capacity, in urine of MSUD patients under protein-restricted diet supplemented or not with L-car capsules at a dose of 50 mg kg(-1) day(-1). It was also determined urinary α-keto isocaproic acid levels as well as blood free L-car concentrations in blood. It was found a deficiency of carnitine in patients before the L-car supplementation. Significant increases of di-tyrosine and isoprostanes, as well as reduced antioxidant capacity, were observed before the treatment with L-car. The L-car supplementation induced beneficial effects on these parameters reducing the di-tyrosine and isoprostanes levels and increasing the antioxidant capacity. It was also showed a significant increase in urinary of α-ketoisocaproic acid after 2 months of L-car treatment, compared to control group. In conclusion, our results suggest that L-car may have beneficial effects in the treatment of MSUD by preventing oxidative damage to the cells and that urine can be used to monitorize oxidative damage in patients affected by this disease.
authors: Faculdade de Farmácia, UFRGS, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
authors: Gilian
authors: G
authors: Guerreiro
authors: Programa de Pós-Graduação em Ciências Biológicas: 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: Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil.
authors: Angela
authors: A
authors: Sitta
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, 90610-000 Porto Alegre, RS, Brazil.
authors: Bruna
authors: B
authors: Donida
authors: Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil.
authors: Desirèe
authors: D
authors: Marchetti
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: Jessica
authors: J
authors: Faverzani
authors: Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil.
authors: Daniella de Moura
authors: Dde M
authors: Coelho
authors: Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035-000 Porto Alegre, RS, Brazil.
authors: Moacir
authors: M
authors: Wajner
authors: Programa de Pós-Graduação em Ciências Biológicas: 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 Ciências Biológicas: 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: D000596:Amino Acids / Q000652:urine; D000704:Analysis of Variance; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D019587:Dietary Supplements; D015237:Dinoprost / Q000031:analogs & derivatives; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000652:urine; D007651:Keto Acids / Q000652:urine; D008297:Male; D008375:Maple Syrup Urine Disease / Q000178:diet therapy / Q000652:urine*; D053719:Tandem Mass Spectrometry; D014443:Tyrosine / Q000652:urine
chemical_list: D000596:Amino Acids; D000975:Antioxidants; D015415:Biomarkers; D028421:Isoprostanes; D007651:Keto Acids; C075750:8-epi-prostaglandin F2alpha; D014443:Tyrosine; D015237:Dinoprost
keywords: Antioxidant; Maple syrup urine disease; Oxidative stress; Urine; l-Carnitine