The Inhibiting Effect of Dinitrosyl Iron Complexes with Thiol-containing Ligands on the Growth of Endometrioid Tumours in Rats with Experimental Endometriosis

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Dinitrosyl iron complexes with glutathione or cysteine fully suppressed endometrioid tumour growth in rats at 20 μmol/kg, but N-acetyl-L-cysteine diminished this effect.

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The paper investigated whether binuclear dinitrosyl iron complexes with thiol-containing ligands—DNIC-GSH (glutathione) and B-DNIC-Cys (cysteine)—could inhibit the growth of endometrioid tumors in rats with surgically induced experimental endometriosis. Rats received intraperitoneal doses and endometrioid tumor (EMT) size and volume were measured; increasing DNIC-GSH or B-DNIC-Cys to 20 μmol/kg fully suppressed growth of implanted uterine tissues, while at 2 μmol/kg the median EMT volume increased and the mean EMT size was larger than controls. When B-DNIC was combined with N-acetyl-L-cysteine (NAC), which is described as able to penetrate cells, the inhibitory effect weakened, with about 30% of implants converting to large-size EMT; the authors discuss possible reasons for this attenuation. This paper is centrally about endometriosis — it tests dinitrosyl iron complexes against growth of endometrioid tumors in a rat model of experimental endometriosis.

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Abstract

The possibility that binuclear dinitrosyl iron complexes with glutathione and cysteine (DNIC-GSН and B-DNIC-Cys) have a strong cytotoxic effect on the growth of endometrioid tumours (EMT) in rats with surgically induced experimental endometriosis established in our previous studies has been supported with experimental data. The increase in the DNIC-GSН or B-DNIC-Cys dose from 10 (in our previous studies) to 20 μmol/kg (after i/p administration to experimental rats) fully suppressed the growth of uterine tissues implanted onto the inner surface of the abdominal wall. At 2 μmol/kg DNIC-GSН, the median value of EMT volume increased from 0 to 15 mm3, while the mean size of EMT-from 55 to 77 mm3 (data from EMT measurements in 10 experimental rats). After treatment of animals with B-DNIC with N-acetyl-L-cysteine (10 μmol/kg) known for its ability to penetrate easily through the cell membrane, the inhibiting effect on EMT growth diminished as could be evidenced from the transformation of ~30% of the implants into large-size EMT. Possible reasons for this phenomenon are discussed.
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Abstract

The possibility that binuclear dinitrosyl iron complexes with glutathione and cysteine (DNIC-GSН and B-DNIC-Cys) have a strong cytotoxic effect on the growth of endometrioid tumours (EMT) in rats with surgically induced experimental endometriosis established in our previous studies has been supported with experimental data. The increase in the DNIC-GSН or B-DNIC-Cys dose from 10 (in our previous studies) to 20 μmol/kg (after i/p administration to experimental rats) fully suppressed the growth of uterine tissues implanted onto the inner surface of the abdominal wall. At 2 μmol/kg DNIC-GSН, the median value of EMT volume increased from 0 to 15 mm3, while the mean size of EMT—from 55 to 77 mm3 (data from EMT measurements in 10 experimental rats). After treatment of animals with B-DNIC with N-acetyl-L-cysteine (10 μmol/kg) known for its ability to penetrate easily through the cell membrane, the inhibiting effect on EMT growth diminished as could be evidenced from the transformation of ~30% of the implants into large-size EMT. Possible reasons for this phenomenon are discussed. Similar content being viewed by others Abbreviations - B- or M-DNIC: - binuclear or mononuclear dinitrosyl iron complexes - Cys: - L-cysteine - EMT: - endometrioid tumours - EPR: - electron paramagnetic resonance - NAC: - N-acetyl-L-cysteine - RNR: - ribonucleotide reductase - RS-NO: - S-nitrosothiol

References

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Acknowledgements

This work has been carried out in the framework of the State Programs of the Russian Federal Agency for Scientific Organizations (0082-2014-0001, No. АААА-A17-117040610310-6 0082-2014-0008 and No. AAAA-A17-117040310008-5). The study is sponsored by Russian academic excellence project “5-100” and supported by the Russian Foundation for Fundamental Research (Grant No. 18-04-00059а) and the Russian Scientific Foundation (Grant No. 16-13-10295). Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Additional information Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Burgovа, E.N., Khristidis, Y.I., Kurkov, A.V. et al. The Inhibiting Effect of Dinitrosyl Iron Complexes with Thiol-containing Ligands on the Growth of Endometrioid Tumours in Rats with Experimental Endometriosis. Cell Biochem Biophys 77, 69–77 (2019). https://doi.org/10.1007/s12013-019-00865-6 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s12013-019-00865-6

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endometriosis

MeSH descriptors

Coordination Complexes Endometriosis Iron Nitrogen Oxides Sulfhydryl Compounds Animals Coordination Complexes Coordination Complexes Cysteine Cysteine Disease Models, Animal Electron Spin Resonance Spectroscopy Endometriosis Endometriosis Female Glutathione Glutathione Iron Ligands Nitric Oxide

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