Physicochemistry of dinitrosyl iron complexes with thiolate ligands underlying their beneficial effect in endometriosis

In: Biophysics · 2014 · vol. 59(4) , pp. 628–634 · doi:10.1134/s0006350914040253 · W2076090688
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Dinitrosyl iron complexes with thiolate ligands exert cytotoxic effects on endometrial tumors in rats with endometriosis by releasing NO and NO+ upon decomposition, similar to their proposed mechanism for inhibiting malignant tumor proliferation.

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The paper reviews the physicochemical basis of exogenous dinitrosyl iron complexes (DNIC) with thiolate ligands as donors of NO and NO+, describing how regulatory effects depend on higher-affinity transfer of NO/NO+ to heme- and thiol-containing biological targets. It argues that DNIC cytotoxicity arises from rapid DNIC decomposition in the presence of iron-chelating compounds, leading to high intracellular and tissue generation of NO and NO+. The authors specifically suggest that this cytotoxic mechanism underlies DNIC’s blocking effect on the development of benign endometrial tumors in rats with experimental endometriosis and may delay malignant tumor proliferation, while noting the general mechanistic nature of these proposals. This paper is centrally about endometriosis — it explains DNIC physicochemistry as the proposed mechanism for beneficial effects in experimental endometriosis models.

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Abstract

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.
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Abstract

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. Similar content being viewed by others

References

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