Effect of original anticonvulsant ortho-fluoro-benzonal on immune cells functional properties at chronic ethanol intoxication

Abstract

IntroductionGABAa-receptors proved to be the molecular targets of ethanol on immune and nervous cells, potentiating alcohol influence. ortho-Fluoro-benzonal is known to be a circular urea derivative and an artificial ligand of GABA/BD-receptor and thus a potential candidate drug for alchoholism treatment.ObjectivesWe have shown the alcohol motivation decrease under ortho-fluoro-benzonal influence in experiment. The investigation of molecular mechanisms and functional targets of this substance is an important step in understanding of molecular pathogenesis and approaches to managing alcohol addiction.MethodsSplenocytes from male (CBAxC57Bl/6) F1 mice in a state of alcohol dependence owing to 6-month 10% ethanol exposure were aseptically obtained and cultured in presence of GABA, ortho-fluoro-benzonal and mitogens (LPS or concanavalin A). Proliferative activity of immune cells in vitro was estimated by means of radioactive 3H-thymidine incorporation.Results The intact animals’ splenocytes revealed increased spontaneous proliferation, increased T-mitogen stimulated and decreased B-mitogen stimulated proliferation in the presence of ortho-fluoro-benzonal. The immune cells from alcoholized animals, demonstrating increased spontaneous proliferative activity and weaken susceptibility to the mitogens, showed normal response patterns, except B-mitogen response case, under ortho-fluoro-benzonal inluence. Addition of GABA into the cultures didn’t cancel most positive effects of ortho-fluoro-benzonal inluence, proving existence of their GABAaR-independent pathways, mediated by other barbiturate receptors in addition to GABAaR-dependent ones.ConclusionsImmunomodulating properties of artificial GABA receptor ligand, ortho-fluoro-benzonal, in vitro has been shown. The compound may correct immune cells dysregulation caused by chronic ethanol exposure, so the original anticonvulsant has promise in the treatment of alcoholism.DisclosureThe authors have not supplied a conflict-of-interest statement.