DNA damage induced by alloisoleucine and other metabolites in maple syrup urine disease and protective effect of l-carnitine.

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: Tatiane Cristina Hauschild, Gilian Guerreiro, Caroline Paula Mescka, Daniella Moura Coelho, Luiza Steffens, Dinara Jaqueline Moura, Vanusa Manfredini, Carmen Regla Vargas
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 57 Pg. 194-202 (Jun 2019) ISSN: 1879-3177 [Electronic] England
• PMID: 30853490 (Publication Type: Controlled Clinical Trial, Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Ltd.

Chemical References

• Amino Acids
• Protective Agents
• 8-Hydroxy-2'-Deoxyguanosine
• Deoxyguanosine
• Carnitine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Amino Acids (administration & dosage, blood, urine)
• Carnitine (therapeutic use)
• Child
• Child, Preschool
• Comet Assay
• DNA Damage
• Deoxyguanosine (analogs & derivatives, urine)
• Dietary Supplements
• Humans
• Maple Syrup Urine Disease (blood, diet therapy, genetics, urine)
• Protective Agents (therapeutic use)