Dipeptide mimetics of nerve growth factor and brain-derived neurotrophic factor, GK-2 and GSB-106 and their cytoprotective properties in the model of oxidative stress

Abstract

Relevance. At the V.V. Zakusov Research Institute of Pharmacology. Zakusov dimeric dipeptide mimetics of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), GK-2 and GSB-106, respectively, were created. GK-2 and GSS-106 were found to be similar to the corresponding full-length neurotrophinsin their mechanism of action and pharmacological properties, including pronounced neuroprotective activity in vitro and in vivo. The aim of this work was to obtain additional data on the cytoprotective properties of GC-2 and GSB-106 using infusoria. Methods. Oxidative stress in Paramecium caudatum was simulated by addition of heavy metal salts (cadmium chloride, lead acetate, copper sulfate, zinc sulfate) to the medium in final concentration of 10 µM. GK-2 or GSB-106 in concentrations from 10-5 to 10-8 M were added to the medium with experimental cells 45 min before the application of oxidative stress initiator. Results. GK-2 and GSB-106 dipeptides in all studied concentrations protected cells from cell death. The maximum neuroprotective effect was shown by dipeptides in concentration of 10-8 M, thus preventing the infusoria death. Conclusion. GK-2 and GSB-106 at a concentration of 10-8 M fully protect Paramecium caudatum from death under oxidative stress induced by heavy metals.