Dinitrosyl iron complexes with glutathione largely relieve rats of experimental endometriosis

A study was made of the effect of binuclear dinitrosyl iron complexes (DNIC) with glutathione in rats with experimental endometriosis. The latter was induced in an autotransplantation model, where two fragments of endometrium with myometrium (2 × 2 mm) from the left uterine horn were grafted to the inner surface of the anterior abdominal wall. After 4 weeks, the test animals received i.p. injections of 0.5 mL DNIC-glutathione at a dose of 12.5 μmol/kg daily for 12 days. This treatment more than halved the total volume of endometrioid tumors. Remarkably, tumor growths from grafts in control rats were often attended by tumors spontaneously arising nearby or in other locations; no such secondary tumors were observed in DNIC-treated animals. The EPR signal with g av = 2.03 characteristic of protein-bound DNIC with thiol ligands was recorded in liver and endometrioid implants of control as well as treated animals. Activation of ribonucleotide reductase, detected by a doublet EPR signal at g = 2.0 with 2.3-mT hyperfine splitting, was found in small tumors. The beneficial effect of DNIC-glutathione was suggested to be due to DNIC breakdown near the tumors, with release of a large amount of molecular nitric oxide and nitrosonium ions that resulted in selective local cytotoxicity. Similar content being viewed by others

B. Eskenazi and M. L. Warner, Obstet Gynecol. Clin. North Am. 24, 235 (1997). A. Asante and R. N. Taylor, Annu. Rev. Physiol. 73, 163 (2011). M. W. Laschke and M. D. Menger, Hum. Reprod. Update (in press). 10.1093/humupd/dms026 (2012). I. G. Campbell and E. J. Thomas, Hum. Reprod. Update 7, 15 (2001). A. Van Langendonckt, J. Donnez, S. Defrere, et al., Mol. Hum. Reprod. 14, 259 (2008). P. Vercellini, P. G. Crosignani, A. Abbiati, et al., Hum. Reprod. Update 15, 177 (2009). E. N. Burgova, L. V. Adamyan, N. A. Tkachev, A. A. Stepanyan, and A. F. Vanin, Biophysics 57, 87 (2012). M. W. Vernon and E. A. Wilson, Fertil. Steril. 44, 684 (1985). L. V. Posiseeva, A. O. Nazarova, I. Yu. Sharabanova, et al., Probl. Reproduktsii, No. 4 (2001). M. S. Cotroneo and C. A. Lamartinier, Pharmacol. Toxicol. Sci. 61, 68 (2001). F. Demirturk, H. Aytan, A. C. Galiskan, et al., J. Soc. Gynecol. Investig. 13(1), (2006). H. Ota, H. Rong, S. Igarashi, et al., Human Reproduction 17, 1453 (2002). K. J. Berkley, in Encyclopedia of Pain (Springer, Berlin, 2007), Part 22, pp. 2640–2644. C. Arnold, J. Lamp, O. Lamp, et al., J. Med. Primatol. 40, 317 (2011). A. F. Vanin, V. A. Serezhenkov, V. D. Mikoyan, et al., Nitric Oxide Biol. Chem. 2, 224 (1997). A. F. Vanin, A. P. Poltorakov, V. D. Mikoyan, et al., Nitric Oxide Biol. Chem. 23, 1236 (2010). M. Fontecave, Cell Mol. Life Sci. 54, 684 (1998). A. V. Murashko, E. N. Burgova, L. V. Adamyan, et al., Biophysics 43, 124 (1998). L. V. Adamyan, S. A. Gasparyan, V. A. Serezhenkov, et al., Akusher. Ginekol., No. 6, 24 (2003). E. N. Burgova, S. A. Gasparyan, G. P. Cheprasova, et al., Probl. Reproduktsii 17, 62 (2011). N. Ya. Giliano, L. V. Konevega, L. A. Noskin, et al., Nitric Oxide Biol. Chem. 24, 151 (2011). R. R. Borodulin, L. N. Kubrina, V. D. Mikoyan, et al., Nitric Oxide Biol. Chem. 29, 4 (2013). L. J. Ignarro, Nitric Oxide: Biology and Pharmacology (Academic Press, San Diego, 2000). K. B. Shumaev, A. A. Gubkin, V. A. Serezhenkov, et al., Nitric Oxide Biol. Chem. 18, 37 (2008). Author information Authors and Affiliations Corresponding author Additional information Original Russian Text © L.V. Adamyan, E.N. Burgova, N.A. Tkachev, V.D. Mikoyan, A.A. Stepanyan, M.M. Sonova, A.V. Galkin, A.F. Vanin, 2013, published in Biofizika, 2013, Vol. 58, No. 2, pp. 302–312. The experimental material reported herein fully corresponds to the original work but the text and data presentation had to be substantially revised for the English version. A.G. Rights and permissions About this article Cite this article Adamyan, L.V., Burgova, E.N., Tkachev, N.A. et al. Dinitrosyl iron complexes with glutathione largely relieve rats of experimental endometriosis. BIOPHYSICS 58, 222–227 (2013). https://doi.org/10.1134/S0006350913020036 Received: Published: Issue date: DOI: https://doi.org/10.1134/S0006350913020036