ABSTRACT
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.
Subject(s)
Iron/chemistry , Nitric Oxide/chemistry , Nitrogen Oxides/chemistry , Saccharomyces cerevisiae/chemistry , Serum Albumin, Bovine/chemistry , Sulfhydryl Compounds/chemistry , Animals , Cattle , Electron Spin Resonance Spectroscopy , Ferrous Compounds/chemistry , Hydrogen-Ion Concentration , Ligands , Mice , Saccharomyces cerevisiae/metabolism , Thiocarbamates/chemistryABSTRACT
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, WistarABSTRACT
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 , RatsABSTRACT
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, WistarABSTRACT
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.
Subject(s)
Acute Kidney Injury/metabolism , Nitric Oxide/biosynthesis , Pregnancy, Animal/metabolism , Animals , Electron Spin Resonance Spectroscopy , Female , Kidney/metabolism , Liver/metabolism , Mice , Organ Specificity , Placenta/metabolism , PregnancySubject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/metabolism , Contrast Media/adverse effects , Kidney/metabolism , Nitric Oxide/biosynthesis , Acute Kidney Injury/prevention & control , Animals , Calcium Channel Blockers/therapeutic use , Electron Spin Resonance Spectroscopy , Rats , Rats, WistarSubject(s)
Ferrous Compounds/metabolism , Leiomyoma/enzymology , Ribonucleotide Reductases/metabolism , Uterine Neoplasms/enzymology , Adult , Electron Spin Resonance Spectroscopy , Female , Humans , Leiomyoma/metabolism , Myometrium/enzymology , Myometrium/metabolism , Nitric Oxide/administration & dosage , Uterine Neoplasms/metabolismSubject(s)
Acute Kidney Injury/metabolism , Contrast Media/toxicity , Diatrizoate Meglumine/toxicity , Nitric Oxide/biosynthesis , Acute Kidney Injury/chemically induced , Acute Kidney Injury/physiopathology , Animals , Calcium Channel Blockers/pharmacology , Kidney/drug effects , Kidney/metabolism , Kidney/physiopathology , Kidney Function Tests , Male , Nitric Oxide Synthase/metabolism , Rats , Rats, Wistar , Verapamil/pharmacologyABSTRACT
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.
Subject(s)
Ditiocarb/chemistry , Ferrous Compounds/chemistry , Animals , Lipopolysaccharides/pharmacology , Male , Mice , Nitrates/metabolism , Nitric Oxide/biosynthesis , Nitrogen Dioxide/metabolismABSTRACT
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.
Subject(s)
Hyperbaric Oxygenation , Mitochondria/metabolism , Animals , Electron Spin Resonance Spectroscopy , Female , Humans , Male , Mice , Mitochondria/analysis , Myocardial Infarction/metabolism , Myocardial Infarction/therapy , Obstetric Labor Complications/metabolism , Obstetric Labor Complications/therapy , Oxidation-Reduction , Pregnancy , Pregnancy Complications/metabolism , Pregnancy Complications/therapy , Rabbits , RatsABSTRACT
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.
Subject(s)
Electron Spin Resonance Spectroscopy , Leiomyoma/enzymology , Ribonucleotide Reductases/analysis , Uterine Neoplasms/enzymology , Uterus/enzymology , Female , HumansABSTRACT
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.
Subject(s)
Electron Spin Resonance Spectroscopy , Endometriosis/analysis , Uterine Neoplasms/analysis , Endometriosis/pathology , Female , Humans , Uterine Neoplasms/pathologyABSTRACT
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.
Subject(s)
Myocardial Infarction/metabolism , Myocardium/metabolism , Transferrin/metabolism , Animals , Electron Spin Resonance Spectroscopy , RabbitsABSTRACT
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.