[Mono- and Binuclear Dinitrosyl Iron Complexes with Thiol-containing Ligands in Various Biosystems].

It has been shown that dinitrosyl iron complexes with thiol-containing ligands, bound with modified bovine serum albumin with high amount of thiol groups, appeared in baker yeast or in animal tissues in the presence of exogenous or endogenous nitric oxide, respectively, are represented predominantly by EPR-silent binuclear form. This form can be transformed into EPR-active mononuclear form of dinitrosyl iron complexes with an increase in pH to basic values, into EPR-active form of mononuclear iron nitrosyl complexes in case of bielectronic recovery of the binuclear form of dinitrosyl iron complexes or under the action of dithiocarbamate derivatives. The latter induced the transformation of dinitrosyl iron complexes into EPR-active mononitrosyl iron complexes with dithiocarbamates. A significant amount of binuclear dinitrosyl iron complexes with thiol-containing ligands in living systems and identical biological activity of these complexes and endogenous nitric oxide systems allow of considering endogenous binuclear dinitrosyl iron complexes as a "working form" of endogenous nitric oxide recognized now as a universal regulator of biological processes.

[Physico-chemistry of dinitrosyl iron complexes with thiol-containing ligands underlying their beneficial treatment of endometriosis].

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.

[Dinitrosyl iron complexes with glutathione recover rats with experimental endometriosis].

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.

[The dinitrosyl-iron complexes with cysteine block the development of experimental endometriosis in rats].

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.

[Nitric oxide production in pregnancy and experimental acute kidney insufficiency]. / Osobennosti produktsii oksida azota pri beremennosti i éksperimental'noi ostroi pochechnoi nedostatochnosti.

Nitric oxide production in organs of pregnant mice (liver, kidney, placenta) was measured using specifical NO traps, Fe-dithiocarbamate complexes (Fe-DETC) forming with NO paramagnetic mononitrosyl iron complexes with DETC (MNIC-DETC), detected by EPR method (-196 degrees C). The amount of NO formed increased in dependence of the pregnancy period (from the first to the third trimesters). Addition of NO-synthase substrate, L-arginine, insignificantly influenced endogenous NO production. However, endogenous NO amount sharply decreased at experimental acute renal failure.

[Hydrophobic and hydrophilic complexes of Fe2+ with dithiocarbamate derivatives as a nitric oxide trap in mice]. / Gidrofobnye i gidrofil'nye kompleksy Fe2+ s proizvodnymi ditiokarbamatakak lovushki oksida azota v organizme myshei.

It has been shown by using EPR method that hydrophobic complexes Fe(2+)-diethyldithiocarbamate (DETC) act more efficiently as a selective traps of nitric oxide (NO) in mice organisms than hydrophilic complexes Fe(2+)-N-methyl-D-glutamyldithiocarbamate (MGD). This difference seemed to be due to higher stability of paramagnetic mononitrosyl iron complexes with DETC (MNIC-DETC) formed in vivo in animal tissues in a result of NO binding with Fe(2+)-DETC complexes. Analogous complexes MNIC-MGD appeared a blood were oxidized to diamagnetic, EPR silent form. The latter was also detected in mouse urine especially for animals which were pretreated with bacterial lipopolysaccharide inducing increased NO generation in mice organisms. Nitrogen dioxide or peroxynitrite formed endogenous NO were suggested to be the agents which oxidized MNIC-MGD by reversible way in mice organisms.

[Effect of the hyperbaric oxygenation of animals and man on mitochondrial function in their tissues (based on EPR study data)]. / Vliianie giperbaricheskoi oksigenatsii zhivotnykh i cheloveka na sostianie mitokhondrii v ikh tkaniakh (po dannym EPR-issledovanii).

The ration of differential intensities of EPR signal of free endogenous radicals of semiquinone type and iron-sulfur proteins recorded at the temperature of liquid nitrogen in tissues (R index) is proposed as a criterion for estimation of changes in the functional state of mitochondria in human and animal tissues treated with hyperbaric oxygenation (HBO). The increase in R value was observed in hearts of intact mice and rabbits treated with HBO in near-toxic doses. This indicates a shift in mitochondria redox state towards oxidation. The above effect was not observed in mitochondria from intact zone of myocardium in animals with experimental infarction, and the numbers of mitochondria in the tissue increased after HBO. HBO treatment of women with pathological pregnancy leads to the decrease in R value for placental mitochondria.

[Paramagnetic form of ribonucleotide reductase in human tissues]. / Paramagnitnaia forma ribonukleotidreduktazy v tkaniakh cheloveka.

The paramagnetic form of ribonucleotide reductase was detected by ESR method in human cervix tissues, especially in tumor ones. The magnetic relaxation rate was proved to be slower for this form than for that in normal animal tissues having a high level of proliferative activity or in Ehrlich tumor cells studied before.

[Electron spin resonance study of the structure of the spin glass type in nodular variant of adenomyosis]. / Issledovanie metodom EPR struktury tipa spinovykh stekol v tkaniakh uzlovatoi formy adenomioza.

Wide ESR signals with g-factor 2.10 (B = 23 mT) and g = 3.0 (B = 80-120 mT) were recorded in the tissues of the nodular form of adenomyosis of women's uterus at the temperature range 20-300 K. The intensity maxima of these signals were at 150 +/- 20 K.

[Increased levels of transferrin in the rabbit heart muscle in experimental myocardial infarction]. / Povyshenie soderzhaniia transferrina v serdechnoi myshtse krolika pri éksperimental'nom infarkte miokarda.

Concentration of transferrin was distinctly increased in the infarction zone of heart muscle of rabbits with experimental myocardium infarction within 24 hrs and 168 hrs after coronary occlusion. Under conditions of cell lysis apotransferrin appears to bind free iron in rabbit heart muscle. The data obtained suggest that apotransferrin may serve as a screening agent of free iron, while caeruloplasmin is able to exhibit the superoxide dismutase activity.

[Effect of hyperbaric oxygenation on paramagnetic centers in the rabbit myocardium during experimental myocardial infarction]. / Vliianie giperbaricheskoi oksigenatsii na paramagnitnye tsentry v myshtse serdtsa krolika pri éksperimental'nom infarkte miokarda.

Changes in paramagnetic centres (PC) concentration in rabbit's myocardial muscle were studied under experimental myocardial infarction during 168 hours by means of ESR-spectroscopy. PC characterized by ESR signal with g = 3.0 was found. It was shown that hyperbaric oxygenation did not affect PC content in the infarction zone, and resulted in an increase of PC concentration with g = 1.94 and g = 2.0 in the intact myocardial zone.