Evaluation of Oxidative Stress Parameters and Energy Metabolism in Cerebral Cortex of Rats Subjected to Sarcosine Administration

Mol Neurobiol. 2017 Aug;54(6):4496-4506. doi: 10.1007/s12035-016-9984-1. Epub 2016 Jun 29.

Abstract

Sarcosine is an N-methyl derivative of the amino acid glycine, and its elevation in tissues and physiological fluids of patients with sarcosinemia could reflect a deficient pool size of activated 1-carbon units. Sarcosinemia is a rare inherited metabolic condition associated with mental retardation. In the present study, we investigated the acute effect of sarcosine and/or creatine plus pyruvate on some parameters of oxidative stress and energy metabolism in cerebral cortex homogenates of 21-day-old Wistar rats. Acute administration of sarcosine induced oxidative stress and diminished the activities of adenylate kinase, GAPDH, complex IV, and mitochondrial and cytosolic creatine kinase. On the other hand, succinate dehydrogenase activity was enhanced in cerebral cortex of rats. Moreover, total sulfhydryl content was significantly diminished, while DCFH oxidation, TBARS content, and activities of SOD and GPx were significantly enhanced by acute administration of sarcosine. Co-administration of creatine plus pyruvate was effective in the prevention of alterations provoked by sarcosine administration on the oxidative stress and the enzymes of phosphoryltransfer network. These results indicate that acute administration of sarcosine may stimulate oxidative stress and alter the energy metabolism in cerebral cortex of rats. In case these effects also occur in humans, they may contribute, along with other mechanisms, to the neurological dysfunction of sarcosinemia, and creatine and pyruvate supplementation could be beneficial to the patients.

Keywords: Cerebral cortex; Energy metabolism; Oxidative stress; Sarcosine; Sarcosinemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism
  • Animals
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology*
  • Creatine Kinase / metabolism
  • Energy Metabolism*
  • Fluoresceins / metabolism
  • Glutathione Peroxidase / metabolism
  • Models, Biological
  • Oxidation-Reduction
  • Oxidative Stress*
  • Rats, Wistar
  • Sarcosine / administration & dosage*
  • Superoxide Dismutase / metabolism

Substances

  • Fluoresceins
  • 2',7'-dichlorodihydrofluorescein
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Creatine Kinase
  • Adenylate Kinase
  • Sarcosine