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Prevention of DNA damage by L-carnitine induced by metabolites accumulated in maple syrup urine disease in human peripheral leukocytes in vitro.
Gene. 2014 Sep 15; 548(2):294-8.GENE

Abstract

Maple syrup urine disease (MSUD) is an inherited aminoacidopathy caused by a deficiency in branched-chain α-keto acid dehydrogenase complex activity that leads to the accumulation of the branched-chain amino acids (BCAAs) leucine (Leu), isoleucine, and valine and their respective α-keto-acids, α-ketoisocaproic acid (KIC), α keto-β-methylvaleric acid, and α-ketoisovaleric acid. The major clinical features presented by MSUD patients include ketoacidosis, failure to thrive, poor feeding, apnea, ataxia, seizures, coma, psychomotor delay, and mental retardation; however, the pathophysiology of this disease is poorly understood. MSUD treatment consists of a low protein diet supplemented with a mixture containing micronutrients and essential amino acids but excluding BCAAs. Studies have shown that oxidative stress may be involved in the neuropathology of MSUD, with the existence of lipid and protein oxidative damage in affected patients. In recent years, studies have demonstrated the antioxidant role of L-carnitine (L-Car), which plays a central function in cellular energy metabolism and for which MSUD patients have a deficiency. In this work, we investigated the in vitro effect of Leu and KIC in the presence or absence of L-Car on DNA damage in peripheral whole blood leukocytes using the alkaline comet assay with silver staining and visual scoring. Leu and KIC resulted in a DNA damage index that was significantly higher than that of the control group, and L-Car was able to significantly prevent this damage, mainly that due to KIC.

Authors+Show Affiliations

Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em CB:Bioquímica e Departamento de Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035-000 Porto Alegre, RS, Brazil. Electronic address: carolmescka@yahoo.com.br.Programa de Pós-Graduação em Ciências Farmacêuticas, 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.Universidade Federal do Pampa, BR 472, Km 585, Caixa Postal 118, 97500-970 Uruguaiana, RS, Brazil.Programa de Pós-Graduação em CB:Bioquímica e Departamento de Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035-000 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 e Departamento de 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.

Pub Type(s)

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

Language

eng

PubMed ID

25046137

Citation

Mescka, Caroline Paula, et al. "Prevention of DNA Damage By L-carnitine Induced By Metabolites Accumulated in Maple Syrup Urine Disease in Human Peripheral Leukocytes in Vitro." Gene, vol. 548, no. 2, 2014, pp. 294-8.
Mescka CP, Wayhs CA, Guerreiro G, et al. Prevention of DNA damage by L-carnitine induced by metabolites accumulated in maple syrup urine disease in human peripheral leukocytes in vitro. Gene. 2014;548(2):294-8.
Mescka, C. P., Wayhs, C. A., Guerreiro, G., Manfredini, V., Dutra-Filho, C. S., & Vargas, C. R. (2014). Prevention of DNA damage by L-carnitine induced by metabolites accumulated in maple syrup urine disease in human peripheral leukocytes in vitro. Gene, 548(2), 294-8. https://doi.org/10.1016/j.gene.2014.07.051
Mescka CP, et al. Prevention of DNA Damage By L-carnitine Induced By Metabolites Accumulated in Maple Syrup Urine Disease in Human Peripheral Leukocytes in Vitro. Gene. 2014 Sep 15;548(2):294-8. PubMed PMID: 25046137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevention of DNA damage by L-carnitine induced by metabolites accumulated in maple syrup urine disease in human peripheral leukocytes in vitro. AU - Mescka,Caroline Paula, AU - Wayhs,Carlos Alberto Yasin, AU - Guerreiro,Gilian, AU - Manfredini,Vanusa, AU - Dutra-Filho,Carlos Severo, AU - Vargas,Carmen Regla, Y1 - 2014/07/18/ PY - 2013/12/03/received PY - 2014/03/31/revised PY - 2014/07/18/accepted PY - 2014/7/22/entrez PY - 2014/7/22/pubmed PY - 2014/10/4/medline KW - Antioxidant-DNA damage KW - Maple syrup urine disease KW - Oxidative stress KW - l-Carnitine SP - 294 EP - 8 JF - Gene JO - Gene VL - 548 IS - 2 N2 - Maple syrup urine disease (MSUD) is an inherited aminoacidopathy caused by a deficiency in branched-chain α-keto acid dehydrogenase complex activity that leads to the accumulation of the branched-chain amino acids (BCAAs) leucine (Leu), isoleucine, and valine and their respective α-keto-acids, α-ketoisocaproic acid (KIC), α keto-β-methylvaleric acid, and α-ketoisovaleric acid. The major clinical features presented by MSUD patients include ketoacidosis, failure to thrive, poor feeding, apnea, ataxia, seizures, coma, psychomotor delay, and mental retardation; however, the pathophysiology of this disease is poorly understood. MSUD treatment consists of a low protein diet supplemented with a mixture containing micronutrients and essential amino acids but excluding BCAAs. Studies have shown that oxidative stress may be involved in the neuropathology of MSUD, with the existence of lipid and protein oxidative damage in affected patients. In recent years, studies have demonstrated the antioxidant role of L-carnitine (L-Car), which plays a central function in cellular energy metabolism and for which MSUD patients have a deficiency. In this work, we investigated the in vitro effect of Leu and KIC in the presence or absence of L-Car on DNA damage in peripheral whole blood leukocytes using the alkaline comet assay with silver staining and visual scoring. Leu and KIC resulted in a DNA damage index that was significantly higher than that of the control group, and L-Car was able to significantly prevent this damage, mainly that due to KIC. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/25046137/Prevention_of_DNA_damage_by_L_carnitine_induced_by_metabolites_accumulated_in_maple_syrup_urine_disease_in_human_peripheral_leukocytes_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(14)00855-5 DB - PRIME DP - Unbound Medicine ER -