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L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD.
Mol Neurobiol. 2016 11; 53(9):6007-6017.MN

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+Show Affiliations

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.Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035-000, Porto Alegre, Rio Grande do Sul, Brazil.Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, 90035-000, Rio Grande do Sul, Brazil.Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, 90035-000, Rio Grande do Sul, Brazil.Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, 90035-000, Rio Grande do Sul, Brazil.Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, 90035-000, 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.Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903, Porto Alegre, Rio Grande do Sul, Brazil.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26526843

Citation

Mescka, Caroline Paula, et al. "L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD." Molecular Neurobiology, vol. 53, no. 9, 2016, pp. 6007-6017.
Mescka CP, Rosa AP, Schirmbeck G, et al. L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD. Mol Neurobiol. 2016;53(9):6007-6017.
Mescka, C. P., Rosa, A. P., Schirmbeck, G., da Rosa, T. H., Catarino, F., de Souza, L. O., Guerreiro, G., Sitta, A., Vargas, C. R., & Dutra-Filho, C. S. (2016). L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD. Molecular Neurobiology, 53(9), 6007-6017. https://doi.org/10.1007/s12035-015-9500-z
Mescka CP, et al. L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD. Mol Neurobiol. 2016;53(9):6007-6017. PubMed PMID: 26526843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD. AU - Mescka,Caroline Paula, AU - Rosa,Andrea Pereira, AU - Schirmbeck,Gabriel, AU - da Rosa,Thales Hein, AU - Catarino,Felipe, AU - de Souza,Laila Oliveira, AU - Guerreiro,Gilian, AU - Sitta,Angela, AU - Vargas,Carmen Regla, AU - Dutra-Filho,Carlos Severo, Y1 - 2015/11/02/ PY - 2015/04/09/received PY - 2015/10/19/accepted PY - 2016/11/1/pubmed PY - 2018/1/16/medline PY - 2015/11/4/entrez KW - Antioxidant KW - Branched-chain amino acids KW - L-carnitine KW - Maple syrup urine disease KW - Neuroprotection KW - Oxidative stress SP - 6007 EP - 6017 JF - Molecular neurobiology JO - Mol Neurobiol VL - 53 IS - 9 N2 - 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. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/26526843/L_carnitine_Prevents_Oxidative_Stress_in_the_Brains_of_Rats_Subjected_to_a_Chemically_Induced_Chronic_Model_of_MSUD_ L2 - https://dx.doi.org/10.1007/s12035-015-9500-z DB - PRIME DP - Unbound Medicine ER -