Tags

Type your tag names separated by a space and hit enter

L-Carnitine supplementation decreases DNA damage in treated MSUD patients.
Mutat Res. 2015 May; 775:43-7.MR

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+Show Affiliations

Programa de Pós-Graduação em CB:Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035 000, Porto Alegre, RS, Brazil. Electronic address: carolmescka@yahoo.com.br.Faculdade de Farmácia, UFRGS, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.Faculdade de Farmácia, UFRGS, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.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.Universidade Federal do Pampa, BR 472, Km 585, Caixa Postal 118, 97500 970 Uruguaiana, RS, Brazil.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; Programa de Pós-Graduação em CB:Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035 000, Porto Alegre, RS, Brazil.Programa de Pós-Graduação em CB:Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, 90035 000, Porto Alegre, RS, Brazil.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.

Pub Type(s)

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

Language

eng

PubMed ID

25867118

Citation

Mescka, Caroline Paula, et al. "L-Carnitine Supplementation Decreases DNA Damage in Treated MSUD Patients." Mutation Research, vol. 775, 2015, pp. 43-7.
Mescka CP, Guerreiro G, Hammerschmidt T, et al. L-Carnitine supplementation decreases DNA damage in treated MSUD patients. Mutat Res. 2015;775:43-7.
Mescka, C. P., Guerreiro, G., Hammerschmidt, T., Faverzani, J., de Moura Coelho, D., Mandredini, V., Wayhs, C. A., Wajner, M., Dutra-Filho, C. S., & Vargas, C. R. (2015). L-Carnitine supplementation decreases DNA damage in treated MSUD patients. Mutation Research, 775, 43-7. https://doi.org/10.1016/j.mrfmmm.2015.03.008
Mescka CP, et al. L-Carnitine Supplementation Decreases DNA Damage in Treated MSUD Patients. Mutat Res. 2015;775:43-7. PubMed PMID: 25867118.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-Carnitine supplementation decreases DNA damage in treated MSUD patients. AU - Mescka,Caroline Paula, AU - Guerreiro,Gilian, AU - Hammerschmidt,Tatiane, AU - Faverzani,Jéssica, AU - de Moura Coelho,Daniella, AU - Mandredini,Vanusa, AU - Wayhs,Carlos Alberto Yasin, AU - Wajner,Moacir, AU - Dutra-Filho,Carlos Severo, AU - Vargas,Carmen Regla, Y1 - 2015/03/28/ PY - 2014/11/18/received PY - 2015/03/19/revised PY - 2015/03/20/accepted PY - 2015/4/14/entrez PY - 2015/4/14/pubmed PY - 2015/6/30/medline KW - Antioxidant KW - DNA damage KW - Maple syrup urine disease KW - Oxidative stress KW - l-Carnitine SP - 43 EP - 7 JF - Mutation research JO - Mutat Res VL - 775 N2 - 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. SN - 1873-135X UR - https://www.unboundmedicine.com/medline/citation/25867118/L_Carnitine_supplementation_decreases_DNA_damage_in_treated_MSUD_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0027-5107(15)00066-4 DB - PRIME DP - Unbound Medicine ER -