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Burgova E.N.,RAS Semenov Institute of Chemical Physics | Tkachev N.A.,RAS Semenov Institute of Chemical Physics | Paklina O.V.,RAS Semenov Institute of Chemical Physics | Mikoyan V.D.,Federal Medical and Biological Agency of Russia | And 2 more authors.
European Journal of Pharmacology | Year: 2014

It has been established that intraperitoneal bolus administration of S-nitrosoglutathione (GS-NO) (12.5 μmoles/kg; 10 injections in 10 days), beginning with day 4 after transplantation of two 2-mm autologous fragments of endometrial tissue onto the inner surface of the abdominal wall of rats with surgically induced (experimenta) endometriosis failed to prevent further growth of endometrioid (EMT) and additive tumors, while treatment of animals with dinitrosyl iron complexes (DNIC) with glutathione (12.5 μmoles/kg, 10 injections in 10 days) suppressed tumor growth virtually completely. The histological analysis of EMT samples of GS-NO-treated rats revealed pathological changes characteristic of control (non-treated with GS-NO or DNIC) rats with experimental endometriosis. EPR studies established the presence of the active form of ribonucleotide reductase, a specific marker for rapidly proliferating tumors, in EMT samples of both control and GS-NO-treated animals. Noteworthy, in small-size EMT and adjacent tissues of DNIC-treated rats the active form of ribonucleotide reductase and pathological changes were not found. © 2014 Elsevier B.V. Source


Ostapenko Y.N.,Federal Biomedical Agency of Russia | Elkis I.S.,Moscow University of Medicine and Dentistry
Terapevticheskii Arkhiv | Year: 2010

The paper considers the pathogenesis, clinical picture, and diagnosis of acute intoxications with alcohol and substitutes, and its prehospital medical care. It details an emergency team's tactics in patients with the above conditions. Source


Vanin A.F.,RAS Semenov Institute of Chemical Physics | Adamyan L.V.,Moscow University of Medicine and Dentistry | Burgova E.N.,RAS Semenov Institute of Chemical Physics | Tkachev N.A.,RAS Semenov Institute of Chemical Physics
Biophysics (Russian Federation) | Year: 2014

Exogenous dinitrosyl iron complexes (DNIC) with thiolate ligands as NO and NO+ donors are capable of exerting both regulatory and cytotoxic effects on diverse biological processes similarly to those characteristic of endogenous nitric oxide. Regulatory activity of DNIC (vasodilatory, hypotensive, suppressing thrombosis, increasing erythrocyte elasticity, accelerating skin wound healing, inducing penile erection, etc.) is determined by their capacity of NO and NO+ transfer to biological targets of the latter (heme- and thiol-containing proteins, respectively) due to higher affinity of the proteins for NO and NO+ than that of DNIC. Cytotoxic activity of DNIC is provided by rapid DNIC decomposition under action of iron-chelating compounds, resulting in appearance of NO and NO+ in cells and tissues in high amounts. The latter mechanism is suggested to cause the blocking effect of DNIC as cytotoxic effectors on the development of benign endometrial tumors in rats with experimental endometriosis. It is also proposed that a similar mechanism can operate to cause at least a delay of malignant tumor proliferation under action of DNIC. © 2014, Pleiades Publishing, Inc. Source


Burgova E.N.,RAS Semenov Institute of Chemical Physics | Tkachev N.A.,RAS Semenov Institute of Chemical Physics | Adamyan L.V.,Moscow University of Medicine and Dentistry | Mikoyan V.D.,RAS Semenov Institute of Chemical Physics | And 3 more authors.
European Journal of Pharmacology | Year: 2014

Dinitrosyl iron complexes (DNIC) with glutathione exert a cytotoxic effect on endometrioid tumours in rats with surgically induced experimental endometriosis. Intraperitoneal treatment of rats (Group 1) with DNIC (12.5 μmoles/kg, daily, for 12 days), beginning with day 4 after the surgical operation (implantation of two 2 mm-thick uterine fragments onto the abdominal wall) 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. The ratio of mean EMI volumes in control and experimental rats of Group 1 was 14:1. In Group 2 rats, the use of a similar treatment protocol 4 weeks after surgery changed this ratio to 1.4:1. Noteworthy, the decrease of this ratio was irrelevant to deceleration of EMI growth at later periods after surgery. The histopathological analysis of EMI samples from experimental rats of Group 2 demonstrated complete disappearance of endometrial cysts suggesting a cytotoxic effect of DNIC on the tumours. The data obtained demonstrate that DNIC with glutathione and, probably, with other thiol-containing ligands hold considerable promise in the design of drugs for treating endometriosis in female patients. © 2014 Elsevier B.V. Source


Adamyan L.V.,Moscow University of Medicine and Dentistry | Burgova E.N.,RAS Semenov Institute of Chemical Physics | Tkachev N.A.,RAS Semenov Institute of Chemical Physics | Mikoyan V.D.,RAS Semenov Institute of Chemical Physics | And 4 more authors.
Biophysics (Russian Federation) | Year: 2013

A study was made of the effect of binuclear dinitrosyl iron complexes (DNIC) with glutathione in rats with experimental endometriosis. The latter was induced in an autotransplantation model, where two fragments of endometrium with myometrium (2 × 2 mm) from the left uterine horn were grafted to the inner surface of the anterior abdominal wall. After 4 weeks, the test animals received i.p. injections of 0.5 mL DNIC-glutathione at a dose of 12.5 μmol/kg daily for 12 days. This treatment more than halved the total volume of endometrioid tumors. Remarkably, tumor growths from grafts in control rats were often attended by tumors spontaneously arising nearby or in other locations; no such secondary tumors were observed in DNIC-treated animals. The EPR signal with gav = 2.03 characteristic of protein-bound DNIC with thiol ligands was recorded in liver and endometrioid implants of control as well as treated animals. Activation of ribonucleotide reductase, detected by a doublet EPR signal at g = 2.0 with 2.3-mT hyperfine splitting, was found in small tumors. The beneficial effect of DNIC-glutathione was suggested to be due to DNIC breakdown near the tumors, with release of a large amount of molecular nitric oxide and nitrosonium ions that resulted in selective local cytotoxicity. © 2013 Pleiades Publishing, Ltd. Source

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