IN VITRO EXPERIMENTAL STUDY OF TISSUE AND CELLULAR TOXICITY OF DRUGS

Abstract

Abstract. We studied the neurotoxic/neurotropic effects of a new derivative of dimethylacetamide and benzoic acid LHT-5-01 in a mixed neuroglial culture to determine both the effect of various concentrations of the compound on cell survival and their interaction with the glutamate noncainate receptor. To do this, a mixed neuroglial culture of the hippocampus of linear newborn (P 1-3) Sprague Dawley rats was resuspended in a neurobasal medium containing 0.5 mmol glutamine, 2% Supplement B27 and 15 μg/ml gentamicin. The cytoplasmic concentration of calcium in the ionized form [Ca2+]i was determined using a Fura-2 fluorescent probe (USA). The viability of culture cells—neurons and glial cells—was determined by the immunocytochemical method. Experimental studies were performed on cultures aged from 7 to 9 days, to which the test compound of dimethylacetamide LHT-5-01 was added at various concentrations in the laboratory of intracellular signaling of the Institute of Cell Biophysics of the Russian Academy of Sciences - a separate division of the Federal State Budgetary Scientific Institution Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences" (Pushchino) in strict accordance with the literary descriptions. Incubation of the culture with 10 μM of the LHT-5-01 compound completely suppresses the first phase of receptor activity, but does not prevent the formation of the second phase of NMDA receptor excitation. The established activity can be considered in the aspect of the prevention of glutamate-mediated excitotoxicity of the test compound.