Hypotensive effect of Oxacom® containing a dinitrosyl iron complex with glutathione: Animal studies and clinical trials on healthy volunteers

Чазов, Е. И.; Rodnenkov, O. V.; Zorin, A. V.; Лакомкин, В. Л.; Gramovich, V. V.; Выборов, О. Н.; Драгнев, А. Г.; Тимошин, А. А.; Buryachkovskaya, L. I.; Абрамов, А. А.; Massenko, Valery P.; Arzamastsev, Evgeny V.; Kapelko, V. I.; Vanin, Anatoly F.

doi:10.1016/j.niox.2012.01.008

Cited by 73 publications

(55 citation statements)

References 20 publications

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“…These studies showed that the toxic dose of the drug exceeds 200-fold its hypotensive dose for rats, but is 800 times lower than that for human beings. The drug did not manifest any mutagenic, allergenic, embryotoxic or teratogenic activity in the dose range under study [33]. Fig.…”

Section: Introductionmentioning

confidence: 72%

“…(4) shows the hypotensive effect of Oxacom on 14 healthy volunteers. A single intravenous injection of DNIC with glutathione at the dose of 0.2 µmoles/kg induced a stable 20-25% decrease of mean arterial pressure, which lasted from 6 to 8 hours and correlated with long-term persistence of DNIC in patients' blood [33].…”

Section: Introductionmentioning

confidence: 86%

“…A slight increase in the level of constrictor hormones as a specific response of the central nervous system to vasodilation immediately after drug injection was the only exception. However, after a course of several hours the blood levels of constrictor hormones dropped down to initial values [33].…”

Section: Introductionmentioning

confidence: 94%

“…Now let us pass to the analysis of hypotensive activity of DNIC with thiol-containing ligands which illustrates their regulatory effect on animal and human organisms. In the past few years, our current attention was focussed on the design of a novel procedure for industrial-scale synthesis of a lyophilized preparation, which represents a dry composite mixture of DNIC with glutathione as a biologically active component and dextran as a filling reagent [33]. This preparation (its commercial name is "Oxacom") has successfully undergone pharmacological trials.…”

Section: Introductionmentioning

confidence: 99%

“…Fig. (3) shows the hypotensive effects of three agents, viz., Oxacom, S-nitrosoglutathione and sodium nitrite after their single intravenous injection to rats at the dose of 0.8 µmoles/kg [33].…”

Section: Introductionmentioning

confidence: 99%

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In-Vitro Antibacterial Activity of Processed Moringa Oleifera Seed Extract: Kill-Time Study

Idris¹,

Muyibi²,

Jamal³

et al. 2013

TOPROCJ

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Some present-day concepts of biological activities of dinitrosyl iron complexes (DNIC) with thiol-containing ligands are reviewed. These activities are determined by the ability of DNIC to act as donors of NO and nitrosonium ions (NO + ) in various body cells and tissues. DNIC are endowed with strong vasodilator activity. Due to the latter DNIC single dose injection into animal and human organisms induces long-lasting hypotension. Moreover, DNIC suppress platelet aggregation, increase red blood cell elasticity, accelerate skin wound healing, induce penis erection in animals and exert pronounced anti-apoptotic effect on cultured non-tumor cells. These regulatory effects are due to the slow release of NO and NO + from intact DNIC at both organism and in cell cultures. Fast decomposition of DNIC, e.g., in the presence of exogenous or endogenous iron-chelating agents, results in a toxic effect of DNIC on various cells and tissues and causes apoptosis of, e.g., HeLa and Jurkat human tumor cells. More recent model studies established the ability of DNIC to suppress endometriosis in rats.

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Section: Introductionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

In-Vitro Antibacterial Activity of Processed Moringa Oleifera Seed Extract: Kill-Time Study

Idris¹,

Muyibi²,

Jamal³

et al. 2013

TOPROCJ

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Dinitrosyl Iron Complexes with Natural Thiol‐Containing Ligands: Physicochemistry, Biology, and Medicine

Vanin

2014

Bioorganometallic Chemistry

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Iron‐sulfur glutaredoxin 2 protects oligodendrocytes against damage induced by nitric oxide release from activated microglia

Lepka

Volbracht

Bill

et al. 2017

Glia

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Demyelinated brain lesions, a hallmark of autoimmune neuroinflammatory diseases like multiple sclerosis, result from oligodendroglial cell damage. Activated microglia are considered a major source of nitric oxide and subsequent peroxynitrite-mediated damage of myelin. Here, we provide biochemical and biophysical evidence that the oxidoreductase glutaredoxin 2 inhibits peroxynitrite formation by transforming nitric oxide into dinitrosyl-diglutathionyl-iron-complexes. Glutaredoxin 2 levels influence both survival rates of primary oligodendrocyte progenitor cells and preservation of myelin structure in cerebellar organotypic slice cultures challenged with activated microglia or nitric oxide donors. Of note, glutaredoxin 2-mediated protection is not linked to its enzymatic activity as oxidoreductase, but to the disassembly of its uniquely coordinated iron-sulfur cluster using glutathione as non-protein ligand. The protective effect of glutaredoxin 2 is connected to decreased protein carbonylation and nitration. In line, brain lesions of mice suffering from experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, show decreased glutaredoxin 2 expression and increased nitrotyrosine formation indicating that this type of protection is missing in the inflamed central nervous system. Our findings link inorganic biochemistry to neuroinflammation and identify glutaredoxin 2 as a protective factor against neuroinflammation-mediated myelin damage. Thus, improved availability of glutathione-coordinated iron-sulfur clusters emerges as a potential therapeutic approach in inflammatory demyelination.

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Hypotensive effect of Oxacom® containing a dinitrosyl iron complex with glutathione: Animal studies and clinical trials on healthy volunteers

Cited by 73 publications

References 20 publications

In-Vitro Antibacterial Activity of Processed Moringa Oleifera Seed Extract: Kill-Time Study

In-Vitro Antibacterial Activity of Processed Moringa Oleifera Seed Extract: Kill-Time Study

Dinitrosyl Iron Complexes with Natural Thiol‐Containing Ligands: Physicochemistry, Biology, and Medicine

Iron‐sulfur glutaredoxin 2 protects oligodendrocytes against damage induced by nitric oxide release from activated microglia

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