Histological and biochemical investigation of antioxidan and antiapoptotic effects of caffeic acid phenethyl ester on Ci̇splati̇n-i̇nduced testi̇cular toxi̇ci̇ty in rats

Cisplatin is a commonly used chemotherapy agent. Cisplatin terminates vital processes such as replication and transcription, and ultimately leads to apoptosis. The cause behind Cisplatin-induced toxicity is the production of reactive oxygen species (ROS) that damage testicular cells, particularly spermatozoa. Polyunsaturated fatty acids, which are susceptible to damage caused by ROS, are the main components of the plasma membrane of the spermatozoan. For this reason, ROS production is a leading cause of male infertility. Recently, alternative therapies in male infertility are a common area of research. Past researches have shown that antioxidants protect spermatozoa from ROS, prevent abnormal spermatozoa production, cleanse the produced ROS, prevent DNA fragmentation, improve sperm quality and prevent premature sperm maturation. In this study, we performed biochemical and histological analyses of the protective and healing effects of Caffeic acid phenethyl ester (CAPE) on Cisplatin-induced testis injury in rats. The study was performed in Wistar albino male rats, 2-3 months old. The experimental groups were divided into four: Kontrol, CAPE, Cisplatin, and Cisplatin+CAPE. For the experimental toxicity model, Cisplatin was dissolved in 0.9% istonic saline solution, and it was given once a day on days 1, 3, and 5, up to 3 mg / kg intraperitoneally. CAPE was dissolved in 2 ml of isotonic saline, and it was given 10 µmol / kg intraperitoneally for 45 days. The rats were sacrificed on the 45th day. Histologically, we observed congestion, thickening, edema, seminiferous tubule structures, vacuolization, hyalinization of connective tissue and interstitial space, irregularities in germinal epithelium, and cell rashes in the interstitial areas of testis tissues belonging to the Cisplatin group. On the other hand, structural disorders and congestion in the Cisplatin + CAPE group were minimal compared to the Cisplatin group. We noted a significant decrease in apoptotic cell count in the Cisplatin + CAPE group compared to the Cisplatin group (p≤0.05). When apoptotic sperm percentages were compared, a significant decrease (p≤0.05) was observed in the Sisplatin + CAPE group compared to the Cisplatin group. As a result of this study, we found that CAPE had a protective effect on Cisplatin-induced testicular toxicity damage and it prevented apoptosis.