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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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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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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

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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).

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Correspondence to Anatoly F. Vanin.

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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

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