Metabolic Brain Disease

, Volume 25, Issue 3, pp 331–338

Creatine prevents the inhibition of energy metabolism and lipid peroxidation in rats subjected to GAA administration

Original Paper

DOI: 10.1007/s11011-010-9215-9

Cite this article as:
Kolling, J. & Wyse, A.T.S. Metab Brain Dis (2010) 25: 331. doi:10.1007/s11011-010-9215-9

Abstract

Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder, biochemically characterized by the tissue accumulation of guanidinoacetate (GAA). Affected patients present epilepsy and mental retardation whose etiopathogeny is unclear. Previous reports have shown that GAA alters brain energy metabolism and that creatine, which is depleted in patients with GAMT deficiency, can act as a neuroprotector; as such, in the present study we investigated the effect of creatine administration on some of the altered parameters of energy metabolism (complex II, Na+,K+-ATPase and creatine kinase) and lipid peroxidation caused by intrastriatal administration of GAA in adult rats. Animals were pretreated for 7 days with daily intraperitonial administrations of creatine. Subsequently, these animals were divided into two groups: Group 1 (sham group), rats that suffered surgery and received saline; and group 2 (GAA-treated). Thirty min after GAA or saline, the animals were sacrificed and the striatum dissected out. Results showed that the administration of creatine was able to reverse the activities of complex II, Na+,K+-ATPase and creatine kinase, as well as, the levels of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation. These findings indicate that the energy metabolism deficit caused by GAA may be prevented by creatine, which probably acts as an antioxidant since it was able to prevent lipid peroxidation. These data may contribute, at least in part, to a better understanding of the mechanisms related to the energy deficit and oxidative stress observed in GAMT deficiency.

Keywords

CreatineGuanidinoacetateGAMT-deficiencyMetabolic disease

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, ICBSUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Laboratório de Erros Inatos do Metabolismo, Departamento de Bioquímica, ICBSUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Departamento de Bioquímica, ICBSUniversidade Federal do Rio Grande do SulPorto AlegreBrazil