EFFECTS OF SILVER NANO-PARTICLES AND RESVERATROL TREATMENT ON FEMALE REPRODUCTIVE FUNCTION UNDER CONDITIONS OF EXPERIMENTAL GLOMERULONEPHRITIS

Kaleinikova O., Sribna V., Stupchuk M., Karvatsky I., Savchuk V., Blashkiv T., Voznesenska T.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Nanomedicine and nanopharmacology are developing at a high race in the search for new drugs. The leading place among them is preparations based on silver nanoparticles (AgNPs). In the progress of autoimmune diseases an important role is played by factors such as hereditary predisposition, adverse effects of environmental factors, immunity disorder. The autoimmune kidney diseases include primary glomerulonephritis (rapidly progressive, chronic, etc.) and glomerulopathy (a large group of diseases), Goodpascher’s syndrome, systemic vasculitis, as well as other systemic autoimmune diseases that are associated with impaired renal function. The purpose of the work – under conditions of experimental glomerulonephritis (EG), to assess the effect of the treatment of the substance AgNPs and resveratrol (RES) on the process of oocyte meiotic maturation stages (metaphase I and metaphase II), on the viability and DNA integrality of the oocyte follicular environment cells (OFECs), as well as pre- and post-implantational embryonic mortality in mice. It was used 56 females and 14 male white laboratory mice (weighing 20-22 g). Experimental glomerulonephritis (EG) in mice was achieved by immunization of white laboratory mice of the first generation with a kidney antigen suspension derived from a parent. Animal immunization was carried out at the rate of 10 mkL of suspension per 10 g of body weight according to the following scheme: 3 times intra-abdominal 1 time per day; re-immunization was carried out after 3 weeks with a single intra-abdominal treatment of the same dose. Characteristics of silver nanoparticles (AgNPs) – size: 30 nm, concentration: 8 mg/ml per metal, shape: spherical, colour: brown, synthesized at the Institute of Biocolloid Chemistry named after F.D. Ovcharenko of the National Academy of Sciences of Ukraine according to the original protocol (chemical condensation method). In the first series animals were divided into the following groups: I – Control (N = 4); II – EG (N = 4); III – AgNPs (N = 4); IV – EG + AgNPs (N = 4); V – RES (N = 4); VI – EG + RES (N = 4); VII – EG + AgNPs + RES (N = 4); N – number of animals in the group. In the second series (group of animals as in the first series). One day after the last injection, males were planted to females in a ratio of 1:2. Were used the method of oocytes cultivation, the method of colour fluorescent dyes, the method of DNA-comets (alkaline), and the method for measuring the pre- and post-implantation embryonic mortality and the statistical analysis methods. It was established that under conditions of EG, both the use of AgNPs and RES weakens the damage in the nuclei of OFECs due to the reduction in their number of single-strand breaks (the effect of AgNPs = RES), and the effect of the treatment of AgNPs and RES (together) – the number of nuclei 0,1 and the third grade is determined by the AgNPs, that is, under the conditions of the EG, the treatment AgNPs+RES has a better effect than a separate AgNPs and separately RES. It was established that the treatment of: 1) AgNPs do not affect the pre- and post-implantation mortality of embryos; 2) AgNPs under conditions of EG – reduces post-implantational embryonic mortality to 1.38±0.37 (p <0.05, n = 6) compared with 5.16±0.63 under the conditions of EG, preimplantation mortality remains unchanged; 3) RES – does not affect the pre- and post-implantation mortality of embryos; 4) RES under conditions of EG – does not affect the magnitude of preimplantation mortality of embryos and reduces post-implantational embryonic mortality to 2.63±0.91 (p <0.05, n = 6), compared with 5.16±0.63 under conditions of EG; 5) AgNPs+RES under conditions of EG do not affect the magnitude of preimplantation mortality of embryos and reduces post-implantational embryonic mortality to 1.87±0.83 (p <0.05, n = 6), compared with 5.16±0.63 under conditions of EG; in comparison with the treatment of AgNPs under the conditions of EG – there are no differences among the middle data groups; in comparison with the treatment of RES under conditions of EG – there are no differences among the middle data groups. Thus, it has been shown that under conditions of the treatment of the substance of the AgNPs, RES and AgNPs+RES, the preimplantation mortality rate does not change and post-implantation – decreases. Future studies can be directed to the establishment of possible mechanisms for the action of nanoparticles (silver) on somatic and germetative cells in appropriate experimental conditions.

oocytes, cells of follicular environment of oocytes, embryos, resveratrol, substance of silver nanoparticles, experimental glomerulonephritis.

1. Lytvynenko A, Rieznichenko L, Sribna V, Stupchuk M, Grushka N, Shepel A, et al. Functional status of reproductive system under treatment of silver nanoparticles in female mice. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2017;6(5):1713-20.
2. Voznesenska TIu, Stupchuk MS, Kaleinikova OM, Sribna VO, Blashkiv TV. Vplyv vnutrishnovennoho vvedennia nanochastynok sribla na ootsyty i klityny yikh folikuliarnoho otochennia v umovakh eksperymentalnoho hlomerulonefrytu. Naukovyi visnyk Skhidnoievropeiskoho natsionalnoho universytetu imeni Lesi Ukrainky. Seriia: biolohichni nauky. 2018;4(377):92-100. [in Ukrainian].
3.  Gilbert S, Weiner D. National Kidney Foundation’s Primer on Kidney Diseases. 6th edition. Elselvier; 2014. 592 р.
4. Kolomeyets NYu, Averianova NI, Kosareva PV, Kolomeyets NYu. Razrabotka modeli khronicheskogo glomerulonefrita u belykh nelineynykh krys. Sovremennyye problemy nauki i obrazovaniya. 2012. Dostupno: www.science-education.ru/103-6454 [in Russian].
5. Paltseva EM. Eksperimentalnyye modeli khronicheskikh zabolevaniy pochek. Klinicheskaya nefrologiya. 2009;2:37-42. [in Russian].
6. Recordati C, De Maglie M, Bianchessi S, Argentiere S, Cella C, Mattiello S, et al. Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects. Part Fibre Toxicol. 2015;13:12.
7. Xue Y, Zhang S, Huang Y, Zhang T, Liu X, Hu Y, et al. Acute toxic effects and gender-related biokinetics of silver nanoparticles following an intravenous injection in mice. J Appl Toxicol. 2012;32:890-9.
8. Reagan-Shaw S, Nihal M, Ahmad N, Reagan-Shaw S. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659-61.
9. De Jong W, Van Der Ven L, Sleijffers A, Park M, Jansen E, Van Loveren H, et al. Systemic and immunotoxicity of silver nanoparticles in an intravenous 28 days repeated dose toxicity study in rats. Biomaterials. 2013;3(34):8333-43.
10. Park K, Park E, Chun I, Choi K, Lee S, Yoon J, et al. Bioavailability and toxicokinetics of citrate-coated silver nanoparticles in rats. Аrch Pharm Res. 2011;34:153-8.
11. Tiedemann D, Taylor U, Rehbock C, Jakobi J, Klein S, Kues W, et al. Reprotoxicity of gold, silver, and gold-silver alloy nanoparticles on mammalian gametes. Analyst. 2014;139(5):931-42.

«Bulletin of problems biology and medicine» Issue 2 Part 1 (150), 2019 year, 129-134 pages, index UDK 612.017:616.36:612.621.1:615.27:611.018

10.29254/2077-4214-2019-2-1-150-129-134