Resumo

Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of guanidinoacetate (GAA). Affected patients present epilepsy and mental retardation whose etiopathogeny is unclear. Since 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, in the present study we investigated the effect of creatine administration on the alterations of some parameters of energy metabolism (complex II, Na+,K+-ATPase and creatine kinase) and lipid peroxidation caused by intrastriatal administration of GAA in male rats sixty 60 days. Animals Wistar were pretreated during seven days with daily intraperitonial administration of creatine (50 mg/kg). During this pretreatment was performed stereotaxic surgery in the animals in order to facilitate the administration of the GAA. Experiments were performed 48 h after surgery. For this, the animals were divided into two groups: Group 1 (sham group), rats that suffered surgery and received saline; and group 2 (GAA-treated), rats that received 10 ìM of GAA solution (0.02 nmol/striatum). The volume administered intrastriatally (saline or GAA solution) was 2 ìL. Thirty min after GAA or saline, the animals were sacrificed by decapitation without anesthesia and striatum dissected out. The findings show that the administration of GAA significantly inhibited complex II (Sal+Sal: 7,57&#+1771,55; GAA+Sal: 4,65&#+1771,01; Crea+Sal: 8,46&#+1771,87; GAA+Crea: 8,38&#+1771,22; n≡5), decreased Na+,K+-ATPase activity (Sal+Sal: 1178,8&#+177331,0; GAA+Sal: 491,4&#+177105,3; Crea+Sal: 1355,2&#+177522,4; GAA+Crea: 1005,6&#+177135,6; n≡5), and creatine kinase activity only on the mitochondrial fraction (Sal+Sal: 0,41&#+1770,072; GAA+Sal: 0,28&#+1770,030; Crea+Sal: 0,41&#+1770,021; GAA+Crea: 0,49&#+1770,11; n≡5), and increased TBARS (Sal+Sal: 1,14&#+1770,14; GAA+Sal: 2,70&#+1770,64; Crea+Sal: 1,14&#+1770,29; GAA+Crea: 1,11&#+1770,42; n≡5). 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. Data are expressed as mean &#+177 SD, Na+,K+-ATPase activity as nmol/ Pi/ min.mg protein, creatine kinase activity as µmol creatine/min/mg protein, complex II activity as nmol/min/mg protein and TBARS as nmol TBARS/ mg protein. These findings indicate that the energy metabolism deficit caused by GAA can be prevented by creatine that probably act 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 found in the GAMT deficiency.