Immunological mechanisms of therapeutic efficacy of oxidized dextran in spermatogenesis disorders of infectious and inflammatory genesis

The article summarizes experimental and clinical data on the immunological properties of oxidized dextran. The study addresses pathophysiological effects of oxidized dextran, in particular, its ability to selectively activate tissue macrophages, including testicular macrophages, which are directly involved in spermatogenesis. In experimental part of the work, a rat model of spermatogenesis disorders was produced by injection of Escherichia coli endotoxin. We have shown that oxidized dextran significantly reduces pathomorphological changes in the testes. At the same time, such effect is associated with the activation of tissue macrophages and release of corresponding cytokines, which exert anti-inflammatory effects and normalize microcirculatory hemodynamics. The presented experimental data correlate with the sufficient results on the high clinical efficacy of oxidized dextran in spermatogenesis disorders and male infertility. Clinical part of this work concerned the effects of rectal administration of oxidized dextran in patients with severe spermatogenesis disorders. It was shown that oxidized dextran significantly increases the volume of ejaculate, the concentration of spermatozoa in the ejaculate, and the total number of spermatozoa. The authors link the data of experimental and clinical studies within the framework of a single concept of tissue macrophage activation and the ability of macrophages to change their phenotype depending on the microenvironment and characteristics of the infectious and inflammatory process. This approach is also confirmed by clinical data on the effect of macrophage phenotypes on drug resistance and severity of intracellular infections, in particular, tuberculosis. Analysis of experimental and clinical data allows the authors to propose a theoretical model for the mechanism of therapeutic effectiveness of oxidized dextran in intracellular infections. The bulk of data presented by the authors allow us to consider oxidized dextran as a quite effective tool for the treatment of intracellular infections, including urogenital infections causing male infertility.

1. Adamyan L.V., Elagin V.V., Kiseleva Yu.Yu., Vechorko V.I., Stepanian A.A., Dashko A.A., Doroshenko D.A. Impact of COVID-19 and other viral infections on male fertility (literature review). Problemy reproduktsii = Russian Journal of Human Reproduction, 2020, Vol. 26, no. 6, pp. 77-82 (In Russ.)

2. Demyashkin G.A., Kogan E.A., Xodzhayan A.B., Demura T.A., Gevandova M.G., Shhekin V.I., Zorin I.A., Boldyrev D.V. Effect of SARS-CoV-2 infections on the male and female reproductive system (meta-analysis). Meditsinskiy vestnik Severnogo Kavkaza = Medical News of North Caucasus, 2020, Vol. 15, no. 4, pp. 582-586. (In Russ.)

3. Kovalyk V.P., Gomberg M.A., Bragina E.E., Yurlov K.I., Kushch A.A. The role of herpes viruses in male infertility. Russkiy meditsinskiy zhurnal. Meditsinskoye obozreniye = Russian Medical Journal. Medical Review, 2021, Vol. 5, no. 3, pp. 123-129. (In Russ.)

4. Kulchavenya E.V. Tuberculosis of the prostate and sexual problems in tuberculosis. Vestnik urologii = Bulletin of Urology, 2014, no. 3, pp. 20-49. (In Russ.)

5. Novikova E.G., Troitsky A.V., Ukah G.U. The use of rectal suppositories with oxidised dextran for calculous prostatitis. Urologiya = Urologiya, 2021, no. 6, pp. 127-129. (In Russ.)

6. Novikova E.G., Troitsky A.V., Ukah G.U., Selyaticzkaya V.G. Experimental study on the efficiency of rectal suppositories with oxidized dextran in patients with benign prostatic hyperplasia. Urologiya = Urologiya, 2021, no. 5, pp. 59-61. (In Russ.)

7. WHO laboratory manual for the examination and processing of human semen/ Translated from English by N.P. Makarova; Scientific editor of the Russian translation L.F. Kurilo. 5th ed. Moscow: Kapital Print, 2012. 291 p.

8. Sapozhkova Zh.Yu., Milovanova G.A., Patsap O.I. Laboratory diagnostics of male infertility. Biomarkers and methods. Part II. Laboratornaya i klinicheskaya meditsina. Farmatsiya = Laboratory and Clinical Medicine. Pharmacy, 2021, Vol. 1, no. 2, pp. 65-79. (In Russ.)

9. Troitskiy A.V., Cherdantseva L.A., Bystrova T.N., Novikova E.G., Uka G.U., Grishin O.V., Lyadov E.A. Prospects for the use of oxidized dextran for the prevention of viral pneumonia and pulmonary fibrosis. Meditsinskiy alyans = Medical Alliance, 2021, Vol. 9, no. 4, pp. 45-53. (In Russ.)

10. Shcherban M.N. Influence of antitubercular and prostatotropic therapies on reproductive system of men with tuberculosis of lungs. Sibirskiy meditsinskiy zhurnal = Siberian Medical Journal, 2008, no. 2, pp. 42-44. (In Russ.)

11. Burrello N., Salmeri M., Perdichizzi A., Bellanca S., Pettinato G., D’Agata R., Vicari E., Calogero A.E. Candida albicans experimental infection: effects on human sperm motility, mitochondrial membrane potential and apoptosis. Reprod. Biomed. Online, 2009, Vol. 18, no. 4, pp. 496-501.

12. Lukyanenko Y.O., Chen J.J., Hutson J.C. Production of 25-hydroxycholesterol by testicular macrophages and its effects on Leydig cells. Biol. Reprod., 2001, Vol. 64, no. 3, pp. 790-796.

13. Figueiredo A.F.A., Wnuk N.T., Vieira C.P., Gonçalves M.F.F., Brener M.R.G., Diniz A.B., Antunes M.M., Castro-Oliveira H.M., Menezes G.B., Costa G.M.J. Activation of C-C motif chemokine receptor 2 modulates testicular macrophages number, steroidogenesis, and spermatogenesis progression. Cell Tissue Res., 2021, Vol. 386, no. 1, pp. 173-190.

14. Yu W., Zheng H., Lin W., Tajima A., Zhang Y., Zhang X., Zhang H., Wu J., Han D., Rahman N.A., Korach K.S., Gao G.F., Inoue I., Li X. Estrogen promotes Leydig cell engulfment by macrophages in male infertility. J. Clin. Invest., 2014, Vol. 124, no. 6, pp. 2709-2721.