The effect of dinitrosyl iron complexes with glutathione and S-nitrosoglutathione on the development of experimental endometriosis in rats: A comparative studies

Burgova, E. N.; Tkachev, N. A.; Paklina, O V; Mikoyan, V. D.; Adamyan, L.V.; Vanin, Anatoly F.

doi:10.1016/j.ejphar.2014.07.017

Cited by 19 publications

(12 citation statements)

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“…The immune status of SNAP-treated rats estimated by interleukin and interpheron content appeared to be notably decreased suggesting enhanced proliferation of EMT. Similar results were obtained in experiments on GS-NO-treated rats [3]. In this case, the effect of GS-NO on rats with surgically induced endometriosis was studied using the same protocol as in experiments on DNIC-Glu-treated rats where GS-NO (12.5 µmoles) was injected beginning with day 4 after surgery; the treatment course lasted 10 days and included 10 injections.…”

Section: Groupmentioning

confidence: 62%

“…Previous studies carried out by the members of our research team at the Semenov Institute of Chemical Physics of the Russian Academy of Sciences have established that exogenous water-soluble Dinitrosyl Iron Complexes (DNIC) with glutathione as Nitric Monoxide donors (NO) can selectively suppress the development of experimental endometriosis in rats induced by surgical transplantation of two 2-mm fragments of uterine tissue onto the inner surface of the abdominal wall [1][2][3]. This effect is manifested in early and more advanced steps of tumor growth.…”

Section: Introductionmentioning

confidence: 99%

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Dinitrosyl Iron Complexes with Glutathione Suppress Surgically Induced Experimental Endometriosis in Rats

Vanin¹

2015

Austin J Reprod Med Infertil

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The review describes the results of our most recent investigations into miscellaneous effects of Dinitrosyl Iron Complexes (DNIC) with Glutathione and S-Nitrosoglutathione (GS-NO) as donors of Nitric Monoxide (NO) on the development of surgically induced endometriosis in rats. Whereas DNIC induced selective suppression of the growth of endometrioid tumors in implantation niduses, GS-NO enhanced tumour growth and lowered the immune responsiveness of experimental rats. It was suggested that the selective cytotoxic action of DNIC with glutathione on endometrioid tumors is a result of DNIC decomposition by endogenous iron chelators generated by tumor cells in order to provide the latter with iron required for fast tumor growth. The nitric monoxide released from DNIC either inside tumor cells or in their vicinity is oxidized to cytotoxic peroxynitrite and thus contributes to the strictly selective cytotoxic effect of DNIC on tumor cells. Such selectivity is not specific to GS-NO whose decomposition is spontaneous and can take place in different divisions of the abdominal cavity.

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Section: Groupmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Dinitrosyl Iron Complexes with Glutathione Suppress Surgically Induced Experimental Endometriosis in Rats

Vanin¹

2015

Austin J Reprod Med Infertil

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“…A common feature of modern endometriosis treatments is the suppression of ovarian hormonal functions in addition to lowering the peripheral estrogen production and efficiency [21]. Because of the side effects resulting from lowered estrogen levels, endometriosis treatment approaches aim to decrease side effects in the reproductive system originating from hormonal treatment using different agents such as dinitrosyl iron complexes [22], kisspeptin antagonists [23], statins [24], protease-activated receptor 2 antagonists [25] and antioxidants [26]. Although endometriosis is not a malign disease, angiogenesis, migration and apoptosis mechanisms are modified in endometriotic tissue [6,27].…”

Section: Discussionmentioning

confidence: 99%

Everolimus as an mTOR Inhibitor Suppresses Endometriotic Implants: an Experimental Rat Study

Kaçan

Yıldız

Kaçan

et al. 2017

Geburtshilfe Frauenheilkd

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Introduction Mammalian target of rapamycin is a pathway to block apoptosis. Recent studies showed that the activity of mammalian target of rapamycin pathway increases in endometriotic lesions. Aim of the present study was to study the effect of everolimus agent, a rapamycin analog, in an experimental endometriosis model. Materials and Methods Endometriosis established by the autotransplantation of uterine tissue in the peritoneal cavity was confirmed in 24 rats. The animals were then randomly divided into three groups to receive either everolimus (1.5?mg/kg/day, p.?o.), anastrozole (0.004?mg/day, p.?o.), or normal saline (0.1?mL, i.?p.) for 14 days. Endometriotic foci were excised, stained with hematoxylin and eosin, and endometriosis was scored semiquantitatively. In addition, immunohistochemical examination were performed using primary antibodies of vascular endothelial growth factor, CD117, and Bax. Results Both anastrozole and everolimus lowered endometriosis scores. Significant decreases in ovarian follicles were observed following anastrozole treatment but not everolimus treatment. Conclusion Through its apoptosis-promoting effect, everolimus suppressed endometriotic foci without negatively affecting ovarian reserve. These findings support the hypothesis that everolimus merits further study on the way to developing a new endometriosis drug.

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“…Similar results illustrating antitumour activities of B-DNIC and GS-NO were obtained in experiments with transplanted adenocarcinoma Ca-755 [56] (Figure 7e,7f). These data suggest that in contrast to non-malignant endometrial tumours (EMT) whose growth was fully suppressed by i/р treatment of rats with 10-fold daily doses of B-DNIC with glutathione (10−12 µmoles/kg) [51][52][53], in mice treated with much higher doses of B-DNIC (100−200 µmoles/kg) short-term (7−11 days) discontinuation of tumour growth was followed by a relapse, the rate of this process exceeding control values (Figure 7). What is the reason for the higher resistance of murine tumour cells to B-DNIC, which in the given experimental series were used as NO donors?…”

Section: Antitumour Effects Of I/p Injected B-dnic With Glutathione In a Model Of Transplanted Murine Solid Lewis Carcinomamentioning

confidence: 91%

Antitumour Activity of Dinitrosyl Iron Complexes with Thiol-Containing Ligands in Animals: An Overview

Vanin¹

2018

Austin J Anal Pharm Chem

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The data reviewed herein strongly suggest that binuclear dinitrosyl iron complexes (DNIC) with glutathione can fully (by 100%) suppress the growth of rapidly proliferating nonmalignant endometrial tumours in rats with experimental endometriosis, on the one hand, and retard the growth of transplanted malignant solid tumours (Lewis lung carcinoma), on the other hand. An inverse correlation was established between the antitumour effect of DNIC with glutathione on Lewis carcinoma and the mode of DNIC administration (intraperitoneal or intravenous). In the former case, the maximum inhibition of tumour growth was achieved by treatment of animals with the highest (200µmoles/kg) dose of DNIC, while after intravenous administration the inhibiting effect of DNIC increased with a decrease of the drug dose to 2µmoles/kg. It was suggested that Lewis carcinoma cells respond to DNIC used as a nitric monoxide (NO) donor by the development of a system of antinitrosative protection similar to that formed in many bacterial species in response to treatment with NO or its derivatives. It is not excluded that DNIC with thiol-containing ligands can fully suppress tumour growth when used as a nitrosonium (NO+) ion (but not NO) donor, as could be evidenced from the results of recent studies by Prof. Liaw et al. [Inorg. Chem. 2016, 55, 9383].

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The effect of dinitrosyl iron complexes with glutathione and S-nitrosoglutathione on the development of experimental endometriosis in rats: A comparative studies

Cited by 19 publications

References 13 publications

Dinitrosyl Iron Complexes with Glutathione Suppress Surgically Induced Experimental Endometriosis in Rats

Dinitrosyl Iron Complexes with Glutathione Suppress Surgically Induced Experimental Endometriosis in Rats

Everolimus as an mTOR Inhibitor Suppresses Endometriotic Implants: an Experimental Rat Study

Antitumour Activity of Dinitrosyl Iron Complexes with Thiol-Containing Ligands in Animals: An Overview

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