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1.
Biophysics (Oxf) ; 67(5): 785-795, 2022.
Article in English | MEDLINE | ID: mdl-36567969

ABSTRACT

The antiviral action of binuclear dinitrosyl iron complexes with glutathione along with diethyldithiocarbamate against the SARS-CoV-2 virus has been demonstrated on a Syrian hamster model after aerosol exposure of SARS-CoV-2-infected animals to the solutions of said compounds. EPR assays in analogous experiments on intact hamsters have demonstrated that the iron complexes and diethyldithiocarbamate are predominantly localized in lung tissues. These results have been compared with similar measurements on intact mice, which have shown the equal localization of these agents in both the lungs and liver. We assume that the release of the nitrosonium cations from the binuclear dinitrosyl iron complexes with glutathione occurs during their contact with diethyldithiocarbamate in the animal body. These cations caused S-nitrosation of host and viral cell proteases, leading to suppression of SARS-CoV-2 infection.

2.
Biophysics (Oxf) ; 67(5): 761-767, 2022.
Article in English | MEDLINE | ID: mdl-36567970

ABSTRACT

This study demonstrates a bacteriostatic effect of binuclear dinitrosyl iron complexes with glutathione on Escherichia coli TN300 cells. It has been quantified by the colony formation assay. The bacteriostatic effect exerted by these complexes increases considerably in the presence of diethyldithiocarbamate. Our results suggest that this effect is caused by the intense release of nitrosonium cations, NO+, from the complexes, which decompose under the action of diethyldithiocarbamate. A similar effect is observed when E. coli cells are treated with diethyldithiocarbamate 40 min after the addition of sodium nitrite or S-nitrosoglutathione. Notably, the level of dinitrosyl iron complexes observed in the bacterial cells due to the effects of sodium nitrite or S-nitrosoglutathione is almost the same as that obtained after treatment with glutathione-containing complexes. The bacteriostatic effects of the NO molecules released from nitrite or S-nitrosoglutathione during their brief interaction with bacteria were significantly smaller than the bacteriostatic effect of NO+. We deduce therefrom that the nitrosonium cations released from DNICs are responsible for the observed bacteriostatic effect of these complexes in E. coli cells.

3.
Biofizika ; 59(4): 766-75, 2014.
Article in Russian | MEDLINE | ID: mdl-25707245

ABSTRACT

Exogenous dinitrosyl iron complexes (DNIC) with thiol-containing 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 (vasodilation, hypotension, trombosis suppression, red blood cell elasticity increasing, skin wound healing acceleration, penile erection inducing, etc) is determined by their capacity of NO and NO+ transfer to biological targets of the latter (hemo- 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 endowed with rapid DNIC decomposition under action of iron-chelating compounds resulting in appearance of NO and NO+ in cells and tissues in high amount. 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 causing at least a delay of malignant tumor proliferation under action of DNIC.


Subject(s)
Endometriosis/drug therapy , Endometriosis/metabolism , Iron/chemistry , Iron/pharmacology , Nitrogen Oxides/chemistry , Nitrogen Oxides/pharmacology , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/pharmacology , Animals , Disease Models, Animal , Endometriosis/pathology , Female , Rats , Rats, Wistar
4.
Biofizika ; 58(2): 295-301, 2013.
Article in Russian | MEDLINE | ID: mdl-23755557

ABSTRACT

The possibility of water-soluble dinitrosyl iron complexes (DNIC) with thiol-containing ligands introduction into lungs and other tissues of mice by free inhalation of little drops (2-3 microns diameter) of the solutions of these complexes was investigated. Little drops of 2-20 mM solutions of the complexes were obtained by using an inhalation apparatus (compressor nebulizer). A cloud of these little drops was then inhaled by animals in a closed chamber. A maximal amount of protein-bound DNICs formed in mouse lungs was 0.6 micromoles per kilogram of tissue weight. The amount of DNIC in lungs, liver and blood decreased to the undetected level within 2-3 hours after inhalation. No cytotoxic effect of DNIC formed in lungs on Mycobacterium tuberculosis was found in mice infected with these mycobacteria.


Subject(s)
Iron/administration & dosage , Liver/drug effects , Lung/drug effects , Nitrogen Oxides/administration & dosage , Administration, Inhalation , Animals , Electron Spin Resonance Spectroscopy , Iron/blood , Ligands , Mice , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/pathogenicity , Nitrogen Oxides/blood , Sulfhydryl Compounds/administration & dosage , Water
5.
Biofizika ; 58(2): 302-12, 2013.
Article in Russian | MEDLINE | ID: mdl-23755558

ABSTRACT

The effect of binuclear dinitrosyl iron complexes (DNIC) with glutathione on endometrioid tumors in rats with experimental endometriosis has been studied. The latter was induced by an autotransplantation model, where two fragments of endometrium with myometrium (2 x 2 mm) from the left uterine horn was grafted to the inner surface of the anterior abdominal wall. The test animals received intraperitoneal injections of 0.5 ml DNIC-glutathione at the dose of 12.5 micromole per kg daily for 12 days 28 days after operation. The injections resulted in more than a 2-fold decrease in the total volume of both large tumors formed from grafts and small additive tumors formed nearby grafts. The disappearance of the additive tumors was also observed in test animals. The EPR signal with g(av) = 2.03 characteristic of protein bound DNIC with thiol-containing ligands was recorded in livers, graft and additive tumors of test and control animals pointing out intensive generation of nitric oxide in rats with experimental endometriosis. Ribonucleotide reductase activation discovered by doublet the EPR signal at g = 2.0 with 2.3 mT hyperfine structure splitting was found in small tumors. The cytotoxic effect of DNIC-glutathione on endometrioid tumors was suggested to be due to DNIC degradation nearby the tumors induced by iron chelating compounds released from the tumors. The degradation resulted in release of a high amount of nitric oxide molecules and nitrosonium ions from DNICs affecting the tumors by way of the cytotoxic effect.


Subject(s)
Endometriosis/drug therapy , Glutathione/administration & dosage , Iron/administration & dosage , Nitric Oxide/metabolism , Nitrogen Oxides/administration & dosage , Animals , Electron Spin Resonance Spectroscopy , Endometriosis/pathology , Endometriosis/surgery , Female , Humans , Ligands , Liver/drug effects , Liver/pathology , Nitrogen Oxides/chemical synthesis , Oxidation-Reduction , Rats
6.
Biofizika ; 57(1): 105-9, 2012.
Article in Russian | MEDLINE | ID: mdl-22567916

ABSTRACT

It has been shown that the administration of 0,5 ml of 5 mM aqueous solution of dinitrosyl-iron complexes (DNIC) with cysteine alleviated the development of experimental endometriosis in rats induced by surgical way: the size of endometriomes decreased 1.85 times when the DNIC was added every day during 10 days. The effect was suggested to be due to cytotoxic action of NO molecules and nitrosonium ions (NO+) released from rapidly decomposed DNIC in animal organism on endometriome tissues.


Subject(s)
Cysteine/administration & dosage , Endometriosis/drug therapy , Iron/administration & dosage , Nitrogen Oxides/administration & dosage , Animals , Cysteine/therapeutic use , Cysts/complications , Cysts/drug therapy , Cysts/pathology , Disease Models, Animal , Electron Spin Resonance Spectroscopy , Endometriosis/complications , Endometriosis/pathology , Female , Injections, Intraperitoneal , Iron/metabolism , Iron/therapeutic use , Nitric Oxide/analysis , Nitric Oxide/metabolism , Nitrogen Oxides/therapeutic use , Rats , Rats, Wistar
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