Dinitrosyl iron complexes with cysteine suppress the development of experimental endometriosis in rats

Dinitrosyl Iron Complexes with Glutathione Suppress Surgically Induced Experimental Endometriosis in Rats

“…Moreover, endometrioid tumors are highly sensitive to cytotoxic effects of DNIC with thiol-containing ligands. In our studies, low (≤ 6 moles/kg) doses of B-DNIC with glutathione strongly suppressed tumor growth in rats even after 10-day treatment [1][2][3]. But how high must the B-DNIC dose be in order to suppress EMT growth in female patients at more advanced steps of the disease?…”

“…It has been established that Nitric Monoxide (NO), one of the simplest chemical compounds synthesized from L-arginine by the enzymatic route in the presence of three isoforms of NO-Synthesis (NOS), functions as one of the most universal regulators of an immense variety of biological processes occurring in human and animal organisms [4]. This activity is usually manifested at micro molar steady-state concentrations of NO synthesized by constitutive isoforms of NOS, viz., the endothelial (eNOS) and neuronal (n-NOS) is forms [1]. At steady-state concentrations of NO ≥100 µM generated by inducible NOS (iNOS), NO molecules, or, more specifically, the product of their interaction with the superoxide, viz., Peroxynitrite (ONOO -) exerts various cytotoxic effects on cells and tissues by acting as a potent effector of cell-mediated immunity [4][5][6].…”

“…Previous studies carried out by the members of our research team at the Semenov Institute of Chemical Physics of the Russian Academy of Sciences have established that exogenous water-soluble Dinitrosyl Iron Complexes (DNIC) with glutathione as Nitric Monoxide donors (NO) can selectively suppress the development of experimental endometriosis in rats induced by surgical transplantation of two 2-mm fragments of uterine tissue onto the inner surface of the abdominal wall [1][2][3]. This effect is manifested in early and more advanced steps of tumor growth.…”

“…The cytotoxic activity of these DNIC was studied cytofluorimetrically by fluorescence quenching of ethidium bromide intercolated into HeLa cell DNA. The fluorescence intensity of DNIC-Glutathione-treated HeLa cells was maintained at a level 1 Potent vasodilatory and hypotensive effects [27][28][29][30][31] 2 Inhibition of platelet aggregation [32][33][34] 3 Antihypoxic effect on the myocardium [35] 4…”

Water-Soluble Dinitrosyl Iron Complex (DNIC): a Nitric Oxide Vehicle Triggering Cancer Cell Death via Apoptosis

“…In vivo, DNICs act as a natural NO carrier to protect cells from the toxic effects of NO, while conserving its physiological properties at lower concentrations of DNICs . Thus, DNIC may be a useful NO carrier that can modulate diverse physiological functions, such as inhibition of platelet aggregation, dilation of vascular smooth muscles via activating soluble guanylate cyclase, and enhancement of cardiac resistance to ischemia. , DNICs at higher concentrations, in another way, may act as mobile NO carriers to conduct NO-related pathological functions, especially in inhibiting carcinogenesis and suppressing the tumor growth via codelivery of nitric oxide and chemotherapeutic agents. , Earlier studies revealed that DNICs could inhibit glutathione reductase and induce heat shock protein (HSP70) expression. − In addition, DNIC-GS were proved to selectively suppress endometriosis in rats − and DNIC-thiosulfate triggered apoptosis in Jurkat cells . Moreover, recent studies demonstrated that the decomposition of DNIC with glutathione or thiosulfate by exogenous Fe 2+ chelators caused apoptotic death of HeLa cells. , The combinational treatment of DNIC ([S 5 Fe­(NO) 2 ] – ) at low concentration and UV-A light induced apoptosis in K562 cells .…”