l-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders

• Published in: Gene Vol. 533; no. 2; pp. 469 - 476
• Main Authors: Ribas, Graziela S., Vargas, Carmen R., Wajner, Moacir
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-01-2014
• Subjects: Animals; Antioxidants; Antioxidants - therapeutic use; Brain Diseases, Metabolic, Inborn - drug therapy; Carnitine - deficiency; Carnitine - pharmacology; Carnitine - therapeutic use; Dietary Supplements; Humans; l-Carnitine; Neurometabolic disorders; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Oxidative stress; Oxidative stress; TAR; PLC; CPT; CNS; MDA; H2O2; BCKAD; Antioxidants; MSUD; PI3K; LCHAD; GSH; MCAD; l-Carnitine; HSP; SOD; TBARS; GPx; VLCAD; Neurometabolic disorders; LC; ROS; CAT; ALC; LCAD; PKU; HD; ATP; HNE; BCAA; HO; acetyl-l-carnitine; malondialdehyde; phenylketonuria; catalase; hydrogen peroxide; central nervous system; superoxide dismutase; phosphoinositol-3 kinase; propionyl-l-carnitine; glutathione peroxidase; very-long-chain acyl-CoA dehydrogenase; maple syrup urine disease; heat shock protein; branched-chain amino acids; branched-chain α-keto acid dehydrogenase complex; carnitine palmitoyltransferase; reduced glutathione; thiobarbituric acid reactive species; reactive oxygen species; 4-hydroxy-2-nonenal; long-chain acyl-CoA dehydrogenase; Huntington's disease; total antioxidant reactivity; medium-chain acyl-coenzyme A dehydrogenase; adenosine triphosphate; long-chain 3-hydroxyacyl-CoA dehydrogenase
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2013.10.017

In recent years increasing evidence has emerged suggesting that oxidative stress is involved in the pathophysiology of a number of inherited metabolic disorders. However the clinical use of classical antioxidants in these diseases has been poorly evaluated and so far no benefit has been demonstrated. l-Carnitine is an endogenous substance that acts as a carrier for fatty acids across the inner mitochondrial membrane necessary for subsequent beta-oxidation and ATP production. Besides its important role in the metabolism of lipids, l-carnitine is also a potent antioxidant (free radical scavenger) and thus may protect tissues from oxidative damage. This review addresses recent findings obtained from patients with some inherited neurometabolic diseases showing that l-carnitine may be involved in the reduction of oxidative damage observed in these disorders. For some of these diseases, reduced concentrations of l-carnitine may occur due to the combination of this compound to the accumulating toxic metabolites, especially organic acids, or as a result of protein restricted diets. Thus, l-carnitine supplementation may be useful not only to prevent tissue deficiency of this element, but also to avoid oxidative damage secondary to increased production of reactive species in these diseases. Considering the ability of l-carnitine to easily cross the blood–brain barrier, l-carnitine supplementation may also be beneficial in preventing neurological damage derived from oxidative injury. However further studies are required to better explore this potential.
•Oxidative stress has been highly demonstrated in neurometabolic disorders.•Carnitine deficiency can cause deleterious effects in the CNS.•Carnitine is a promising antioxidant in the treatment of neurometabolic disorders.