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. doi: 10.1016/j.gene.2014.07.051. Epub 2014 Jul 18.


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.

Keywords: Antioxidant-DNA damage; Maple syrup urine disease; Oxidative stress; l-Carnitine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carnitine / pharmacology*
  • Comet Assay
  • DNA Damage / drug effects*
  • Energy Metabolism / drug effects
  • Humans
  • Keto Acids / metabolism*
  • Leucine / metabolism*
  • Leukocytes / metabolism
  • Maple Syrup Urine Disease / metabolism*
  • Maple Syrup Urine Disease / pathology
  • Oxidative Stress
  • Vitamin B Complex / pharmacology*


  • Keto Acids
  • Vitamin B Complex
  • Leucine
  • Carnitine