Creatine Amides: Perspectives for Neuroprotection
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The neuroprotective activity of creatine amides – amino acid derivatives of creatine – was studied in a model of cerebral ischemia created by transient occlusion of the middle cerebral artery (OMCA) in rats. The neuroprotective effect of treatment with glycine (creatinylglycine ethyl ester acetate), phenylalanine (creatinyl-L-phenylalaninamide acetate), tyrosine (creatinyl-L-tyrosinamide acetate), and gamma-aminobutyric acid (creatinyl-γ-aminobutyric acid ethyl ester acetate) derivatives were studied after administration 1 h before 30-min cerebral ischemia. Brain damage was assessed by staining brain slices with triphenyltetrazolium chloride 48 h after ischemia. As compared with the control group, all the creatine amides studied significantly decreased the sizes of areas of brain damage (p < 0.05). However, the amides of creatine with tyrosine, phenylalanine, and GABA showed marked toxicity after intravenous administration and could only be used intraperitoneally. The amide of creatine and glycine was not toxic on administration of intravenous boluses at a dose of 1 mmol/kg. Conclusions: amides of creatine and amino acids decrease ischemic damage after transient occlusion of the middle cerebral artery in rats.
Keywordscreatine derivatives cerebral ischemia neuroprotection
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- 1.S. V. Burov and A. N. Khromov, Russian Federation Patent No. 2354645, “Creatine amides, methods of preparation, substances with neuroprotective actions.”Google Scholar
- 2.O. I. Pisarenko, V. S. Shul'zhenko, I. M. Studneva, and M. G. Lepilin, “Effects of metabolic substrates and mannitol on the efficacy of protection against cardioplegia in isolate rat heart,” Kardiologiya, No. 1, 71–75 (2003).Google Scholar
- 4.R. F. Abett, M. MacMillan, M. J. Sole, et al., “Free tyrosine levels of rat brain and tissues with sympathetic innervation following administration of L-tyrosine in the presence and absence of large neutral amino acids,” J. Nutr., 114, No. 5, 835–839 (1984).Google Scholar
- 12.P. Lipton, “Ischemic cell death in brain neurons,” Physiol. Rev., 79, No. 4, 1421–1685 (1999).Google Scholar
- 21.G. S. Salomons and M. Wyss (eds.), Creatine and Creatine Kinase in Health and Disease, Springer (2007).Google Scholar