Pharmacology

Biography

Biography: Evgenia

Abstract

It has been established that mononuclear and binuclear dinitrosyl iron complexes (DNIC) with thiol-containing ligands (cysteine or glutathione – RS) (formulas {(RS-)2Fe+(NO+)2+ and (RS-)2Fe2+(NO+)42+}, respectively), produce miscellaneous physiological and biochemical effects on animal and human cells and tissues. Their biological action mimics that of nitrogen monoxide (NO), a universal endogenous regulator of metabolic processes, and its oxidized form, viz., nitrosonium ion (NO+), and is based on the ability of DNIC to act as NO and NO+ donors in biological systems. By acting as NO+ donors, DNIC with thiol-containing ligands initiate S-nitrosation of thiol-containing proteins responsible for programmed cell death. Intraperitoneal treatment of rats DNIC with glutathione (12.5 moles/kg, 10 injections in 10 days), beginning with day 4 after the surgical operation (model of peritoneal endometriosis), followed by 14-day keeping of animals on a standard feeding schedule without medication resulted in complete inhibition of the growth of endometrioid implants (EMI) in the majority of experimental animals. A comparison of effects of DNIC and GS-NO on the growth of EMI demonstrated their effects opposite on EMI; while DNIC effectively suppressed tumour growth, GS-NO failed to produce such an effect. General toxic effect of the latter was manifested in the uninterrupted growth of EMI and the appearance of peritoneal adhesions. An EPR study of EMI tissues of control rats established the presence of endogenous DNIC with thiol-containing ligands with a characteristic EPR peak at g = 2.04 resulting from enhanced generation of NO in cells and tissues of these animals. Another important finding of this study, viz., detection of an active form of ribonucleotide reductase (RNR) in EMI samples of control rats by a characteristic doublet EPR signal at g = 2.0 and splitting of 2.2 mT, provided additional evidence in favour of enhanced rates of proliferative processes in endometrial tissues of these animals. Very small concentration of RNR form was detected during EPR analysis of EMI samples of experimental rats.