Experimental study of the antigenotoxic properties of prostagenin in rat testicular tissue cells using the DNA comet method

Abstract

Introduction. There has been a sharp decline in male fertility over the past few decades. Men are unable to conceive, despite ideal sperm analysis in 15-40% of cases. Most of them have increased sperm DNA fragmentation. Testicular oxidative stress is one of the causes of this pathology. Germline DNA damage associated with testicular stress can be reduced by antioxidants. However, their effectiveness currently does not exceed 10%. The search for more effective means of this kind is relevant. The aim of this study was to evaluate the antigenotoxic properties of prostagenin in the DNA comet test in rat and mouse testicular tissue cells.

Methodology.  The experiments were performed on male C57Bl/6 mice (2.5 months old, n=45) and male SD rats (4 months old, n=20). The experimental studies were divided into 4 series. Paclitaxel was used as a model of DNA damage in the first two series, etoposide in the third, and doxorubicin in the fourth. All cytostatic drugs were administered intravenously at the maximum tolerated dose, once. Prostagnin was administered intragastrically to mice at a dose of 23 mg/kg, and to rats - 10 mg/kg. Animals received PG 5 days before and 5 days after the administration of the cytostatic drug. The cytostatic drug was administered to male mice in the first, third and fourth series of experiments, in the second series - to male rats. Animals were sacrificed the day after PG administration in the 1st and 4th series and in the 2nd and 3rd series - on the 90th day after administration of the test compound. The testes were removed for further DNA damage analysis after euthanasia. DNA breaks in testicular cells were quantified using the comet assay. The percentage of DNA in the tail (% tail DNA) was used as an indicator of DNA damage.

Results. The introduction of prostagenin resulted in a statistically significant antigenotoxic effect in all the studied series. The degree of its expression varied from 38.5 (paclitaxel, etoposide) to 52% (doxorubicin). The conducted studies allow us to consider it appropriate to further study the genoprotective activity of prostagenin in a wider range of therapeutic doses.

Conclusion. Thus, it was established, that the antioxidant drug prostagenin has a genoprotective effect in experimental models of DNA fragmentation, caused by different types of cytostatic effects as a result of the conducted studies. Its effectiveness as a genoprotector should be proven in clinical trials.