Oxidative damage in glutaric aciduria type I patients and the protective effects of l-carnitine treatment

J Cell Biochem. 2018 Dec;119(12):10021-10032. doi: 10.1002/jcb.27332. Epub 2018 Aug 20.


The deficiency of the enzyme glutaryl-CoA dehydrogenase, known as glutaric acidemia type I (GA-I), leads to the accumulation of glutaric acid (GA) and glutarilcarnitine (C5DC) in the tissues and body fluids, unleashing important neurotoxic effects. l-carnitine (l-car) is recommended for the treatment of GA-I, aiming to induce the excretion of toxic metabolites. l-car has also demonstrated an important role as antioxidant and anti-inflammatory in some neurometabolic diseases. This study evaluated GA-I patients at diagnosis moment and treated the oxidative damage to lipids, proteins, and the inflammatory profile, as well as in vivo and in vitro DNA damage, reactive nitrogen species (RNS), and antioxidant capacity, verifying if the actual treatment with l-car (100 mg kg-1 day-1 ) is able to protect the organism against these processes. Significant increases of GA and C5DC were observed in GA-I patients. A deficiency of carnitine in patients before the supplementation was found. GA-I patients presented significantly increased levels of isoprostanes, di-tyrosine, urinary oxidized guanine species, and the RNS, as well as a reduced antioxidant capacity. The l-car supplementation induced beneficial effects reducing these biomarkers levels and increasing the antioxidant capacity. GA, in three different concentrations, significantly induced DNA damage in vitro, and the l-car was able to prevent this damage. Significant increases of pro-inflammatory cytokines IL-6, IL-8, GM-CSF, and TNF-α were shown in patients. Thus, the beneficial effects of l-car presented in the treatment of GA-I are due not only by increasing the excretion of accumulated toxic metabolites, but also by preventing oxidative damage.

Keywords: DNA damage; glutaric aciduria type I; glutaryl-CoA dehydrogenase; inflammation; l-carnitine; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / metabolism*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Brain Diseases, Metabolic / metabolism*
  • Carnitine / pharmacology*
  • Carnitine / therapeutic use
  • Child
  • Child, Preschool
  • DNA Damage*
  • Female
  • Glutaryl-CoA Dehydrogenase / deficiency*
  • Glutaryl-CoA Dehydrogenase / drug effects
  • Glutaryl-CoA Dehydrogenase / metabolism
  • Humans
  • Infant
  • Male
  • Oxidative Stress*
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • Reactive Nitrogen Species


  • Antioxidants
  • Protective Agents
  • Reactive Nitrogen Species
  • Glutaryl-CoA Dehydrogenase
  • Carnitine

Supplementary concepts

  • Glutaric Acidemia I