Biological activity of a drug, polypeptides derived from testes in a model of oxidative stress in vitro.

Abstract

Introduction. Male infertility is one of the main causes of forced childlessness of couples around the world. Currently, a limited number of drugs for the treatment of male infertility are available on the market. Biologically active supplements (dietary supplements) containing L-carnitine are often used in the complex therapy. The results of determining the therapeutic activity of a new drug, a peptide complex obtained from cattle testes (PP-R-001) for the treatment of male infertility and comparing its effectiveness with L-carnitine in the models of oxidative stress induction in cell cultures are presented. Material and methods. The study was carried out on cell lines of transplanted piglet testicle (PTP) and bovine embryonic testicle (TEB). Two experimental approaches were used to induce oxidative stress (OS) in testicular cells: co-culturing cells of either PTP or TEB with cisplatin (cis-Pt) or hydrogen peroxide (H2O2). The protective effect of the PP-R-001 peptide complex was assessed by the induction of apoptosis and testicular cell death, migration activity, the number of cells with DNA double-strand breaks, the level of reactive oxygen species, mitochondrial activity of cells under OS conditions. Results. The effect of PP-R-001 significantly exceeded the effect of L-carnitine on the survival rate and decrease of apoptotic cell number of PTP and TEB under OS conditions. PP-R-001 significantly increased the migration activity of both cell lines. It was found that PP-R-001 significantly reduced the level of intracellular lesions that lead to apoptotic death of TEB and PTP cells exposed to both cis-Pt and H2O2: the drug increased the activity of mitochondria and decreased the number of DNA double-strand breaks and reactive oxygen species (ROS). Conclusion. The data obtained indicate that PP-R-001 has a multimodal effect on testicular TEB and PTP cells in the oxidative stress models, which is superior to the effect of L-carnitine widely used in male fertility supplements.