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DNA damage induced by alloisoleucine and other metabolites in maple syrup urine disease and protective effect of l-carnitine.
Toxicol In Vitro. 2019 Jun; 57:194-202.TV

Abstract

Maple syrup urine disease (MSUD) is an inherited deficiency of the branched-chain α-keto dehydrogenase complex, characterized by accumulation of the branched-chain amino acids (BCAAs) and their respective branched chain α-keto-acids (BCKAs), as well as by the presence of alloisoleucine (Allo). Studies have shown that oxidative stress is involved in the pathophysiology of MSUD. In this work, we investigated using the comet assay whether Allo, BCAAs and BCKAs could induce in vitro DNA damage, as well as the influence of l-Carnitine (L-Car) upon DNA damage. We also evaluated urinary 8-hydroxydeoguanosine (8-OHdG) levels, an oxidative DNA damage biomarker, in MSUD patients submitted to a restricted diet supplemented or not with L-Car. All tested concentrations of metabolites (separated or incubated together) induced in vitro DNA damage, and the co-treatment with L-Car reduced these effects. We found that Allo induced the higher DNA damage class and verified a potentiation of DNA damage induced by synergistic action between metabolites. In vivo, it was observed a significant increase in 8-OHdG levels, which was reversed by L-Car. We demonstrated for the first time that oxidative DNA damage is induced not only by BCAAs and BCKAs but also by Allo and we reinforce the protective effect of L-Car.

Authors+Show Affiliations

Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil; Serviço de Genéstica Médica, HCPA, R. Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: tatianehauschild@hotmail.com.Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil; Serviço de Genéstica Médica, HCPA, R. Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil.Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil.Serviço de Genéstica Médica, HCPA, R. Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil.Laboratório de Genética Toxicológica, UFCSPA, R. Sarmento Leite, 245, CEP 90050-170 Porto Alegre, RS, Brazil.Laboratório de Genética Toxicológica, UFCSPA, R. Sarmento Leite, 245, CEP 90050-170 Porto Alegre, RS, Brazil.Programa de Pós-Graduação em Bioquímica, BR 472, Km 585, 118, Universidade Federal do Pampa, CEP 97500-970 Uruguaiana, RS, Brazil.Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, R. Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil; Serviço de Genéstica Médica, HCPA, R. Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: crvargas@hcpa.edu.br.

Pub Type(s)

Controlled Clinical Trial
Journal Article

Language

eng

PubMed ID

30853490

Citation

Hauschild, Tatiane Cristina, et al. "DNA Damage Induced By Alloisoleucine and Other Metabolites in Maple Syrup Urine Disease and Protective Effect of L-carnitine." Toxicology in Vitro : an International Journal Published in Association With BIBRA, vol. 57, 2019, pp. 194-202.
Hauschild TC, Guerreiro G, Mescka CP, et al. DNA damage induced by alloisoleucine and other metabolites in maple syrup urine disease and protective effect of l-carnitine. Toxicol In Vitro. 2019;57:194-202.
Hauschild, T. C., Guerreiro, G., Mescka, C. P., Coelho, D. M., Steffens, L., Moura, D. J., Manfredini, V., & Vargas, C. R. (2019). DNA damage induced by alloisoleucine and other metabolites in maple syrup urine disease and protective effect of l-carnitine. Toxicology in Vitro : an International Journal Published in Association With BIBRA, 57, 194-202. https://doi.org/10.1016/j.tiv.2019.03.007
Hauschild TC, et al. DNA Damage Induced By Alloisoleucine and Other Metabolites in Maple Syrup Urine Disease and Protective Effect of L-carnitine. Toxicol In Vitro. 2019;57:194-202. PubMed PMID: 30853490.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DNA damage induced by alloisoleucine and other metabolites in maple syrup urine disease and protective effect of l-carnitine. AU - Hauschild,Tatiane Cristina, AU - Guerreiro,Gilian, AU - Mescka,Caroline Paula, AU - Coelho,Daniella Moura, AU - Steffens,Luiza, AU - Moura,Dinara Jaqueline, AU - Manfredini,Vanusa, AU - Vargas,Carmen Regla, Y1 - 2019/03/07/ PY - 2018/11/19/received PY - 2019/03/01/revised PY - 2019/03/05/accepted PY - 2019/3/12/pubmed PY - 2019/5/24/medline PY - 2019/3/12/entrez KW - Alloisoleucine KW - DNA damage KW - Maple syrup urine disease KW - Oxidative stress KW - l-carnitine SP - 194 EP - 202 JF - Toxicology in vitro : an international journal published in association with BIBRA JO - Toxicol In Vitro VL - 57 N2 - Maple syrup urine disease (MSUD) is an inherited deficiency of the branched-chain α-keto dehydrogenase complex, characterized by accumulation of the branched-chain amino acids (BCAAs) and their respective branched chain α-keto-acids (BCKAs), as well as by the presence of alloisoleucine (Allo). Studies have shown that oxidative stress is involved in the pathophysiology of MSUD. In this work, we investigated using the comet assay whether Allo, BCAAs and BCKAs could induce in vitro DNA damage, as well as the influence of l-Carnitine (L-Car) upon DNA damage. We also evaluated urinary 8-hydroxydeoguanosine (8-OHdG) levels, an oxidative DNA damage biomarker, in MSUD patients submitted to a restricted diet supplemented or not with L-Car. All tested concentrations of metabolites (separated or incubated together) induced in vitro DNA damage, and the co-treatment with L-Car reduced these effects. We found that Allo induced the higher DNA damage class and verified a potentiation of DNA damage induced by synergistic action between metabolites. In vivo, it was observed a significant increase in 8-OHdG levels, which was reversed by L-Car. We demonstrated for the first time that oxidative DNA damage is induced not only by BCAAs and BCKAs but also by Allo and we reinforce the protective effect of L-Car. SN - 1879-3177 UR - https://www.unboundmedicine.com/medline/citation/30853490/DNA_damage_induced_by_alloisoleucine_and_other_metabolites_in_maple_syrup_urine_disease_and_protective_effect_of_l_carnitine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0887-2333(18)30735-5 DB - PRIME DP - Unbound Medicine ER -