caa a22 4500 606233997 CHVBK 20210128101235.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s11010-014-2322-x doi (NATIONALLICENCE)springer-10.1007/s11010-014-2322-x Increased oxidative stress in patients with 3-hydroxy-3-methylglutaric aciduria [Elektronische Daten] [Mariana dos Santos Mello, Graziela Ribas, Carlos Wayhs, Tatiane Hammerschmidt, Gilian Guerreiro, Jéssica Favenzani, Ângela Sitta, Daniella de Moura Coelho, Moacir Wajner, Carmen Vargas] 3-hydroxy-3-methylglutaric aciduria (HMGA; OMIM 246450) is a rare autosomal recessive disorder, caused by the deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase (4.1.3.4), which results in the accumulation of3-hydroxy-3-methylglutaric (HMG) and 3-methylglutaric (MGA) acids in tissues and biological fluids of affected individuals. Recent in vivo and in vitro animal studies have demonstrated that the accumulation of these metabolites can disturb the cellular redox homeostasis, which can contribute to the neurological manifestations presented by the patients. So, in the present work, we investigated oxidative stress parameters in plasma and urine samples from HMGA patients, obtained at the moment of diagnosis of this disorder and during therapy with low-protein diet and L-carnitine supplementation. It was verified that untreated HMGA patients presented higher levels of urinary di-tyrosine and plasma thiobarbituric acid-reactive substances (TBA-RS), which are markers of protein and lipid oxidative damage, respectively, as well as a reduction of the urinary antioxidant capacity. Treated HMGA patients also presented an increased protein oxidative damage, as demonstrated by their higher concentrations of plasma protein carbonyl groups and urinary di-tyrosine, as well as by the reduction of total sulfhydryl groups in plasma, in relation to controls. On the other hand, HMGA patients under therapy presented normal levels of TBA-RS and urinary antioxidant capacity, which can be related, at least in part, to the antioxidant and antiperoxidative effects exerted by L-carnitine. The results of this work are the first report showing that a redox imbalance occurs in patients with HMGA what reinforces the importance of the antioxidant therapy in this disorder. Springer Science+Business Media New York, 2015 3-hydroxy-3-methylglutaricaciduria nationallicence Organic acidurias nationallicence Carnitine nationallicence Oxidative stress nationallicence Oxidative damage nationallicence dos Santos Mello Mariana Programa de Pós-Graduação Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul (UFRGS), Ipiranga 2752, 90610-000, Porto Alegre, RS, Brazil aut Ribas Graziela Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut Wayhs Carlos Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut Hammerschmidt Tatiane Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut Guerreiro Gilian Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut Favenzani Jéssica Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut Sitta Ângela Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut de Moura Coelho Daniella Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut Wajner Moacir Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut Vargas Carmen Programa de Pós-Graduação Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul (UFRGS), Ipiranga 2752, 90610-000, Porto Alegre, RS, Brazil aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 402/1-2(2015-04-01), 149-155 0300-8177 402:1-2<149 2015 402 11010 https://doi.org/10.1007/s11010-014-2322-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2322-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- dos Santos Mello Mariana Programa de Pós-Graduação Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul (UFRGS), Ipiranga 2752, 90610-000, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Ribas Graziela Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Wayhs Carlos Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Hammerschmidt Tatiane Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Guerreiro Gilian Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Favenzani Jéssica Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Sitta Ângela Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- de Moura Coelho Daniella Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Wajner Moacir Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Bairro: Bom Fim, 90035-903, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Vargas Carmen Programa de Pós-Graduação Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul (UFRGS), Ipiranga 2752, 90610-000, Porto Alegre, RS, Brazil aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 402/1-2(2015-04-01), 149-155 0300-8177 402:1-2<149 2015 402 11010