Adeyanju Anne A, Oyenihi Omolola R, Oguntibeju Oluwafemi O, Ojomu Oreoluwa
Faculty of Applied Sciences, Department of Biological Sciences, Koladaisi University, Ibadan, Nigeria.
Phytomedicine and Phytochemistry Group, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville, South Africa.
Drug Chem Toxicol. 2023 Mar;46(2):219-225. doi: 10.1080/01480545.2021.2018455. Epub 2021 Dec 29.
Male reproductive toxicity is a well-established side effect of the chemotherapeutic drug adriamycin (ADR). Sildenafil (SIL) is a phosphodiesterase inhibitor known to enhance the chemosensitivity of cancer cells to ADR. However, there is a scarcity of information on the effect of SIL on ADR-induced testicular toxicity. In this study, SIL (5, 10, or 20 mg/kg/day) was administered to male rats for 7 days, followed by a single intraperitoneal injection of ADR (20 mg/kg) on day 7. Control rats received either ADR, SIL, or normal saline for 7 days. Epididymal sperm were collected from the testes to assess the effects on sperm quality, quantity, and serum testosterone concentration was also determined. ADR treatment caused a decrease in sperm motility and elevated the percentage of sperms with tail defects which worsened in combination with SIL (20 mg/kg). Furthermore, ADR alone or in combination with SIL dose-dependently increased total sperm abnormalities. SIL (20 mg/kg) plus ADR also decreased sperm count and lowered testosterone level compared to ADR-only rats. In conclusion, exposure of rats to SIL before ADR treatment has the potential to worsen ADR-induced testicular toxicity.
男性生殖毒性是化疗药物阿霉素（ADR）一种已被充分证实的副作用。西地那非（SIL）是一种磷酸二酯酶抑制剂，已知可增强癌细胞对ADR的化学敏感性。然而，关于SIL对ADR诱导的睾丸毒性影响的信息却很匮乏。在本研究中，给雄性大鼠连续7天给予SIL（5、10或20毫克/千克/天），然后在第7天腹腔注射一次ADR（20毫克/千克）。对照大鼠连续7天接受ADR、SIL或生理盐水。从睾丸收集附睾精子以评估对精子质量和数量的影响，同时还测定血清睾酮浓度。ADR处理导致精子活力下降，尾部缺陷精子的百分比升高，与SIL（20毫克/千克）联合使用时情况恶化。此外，单独使用ADR或与SIL联合使用均剂量依赖性地增加总精子异常率。与仅接受ADR的大鼠相比，SIL（20毫克/千克）加ADR还降低了精子数量并降低了睾酮水平。总之，在ADR治疗前让大鼠接触SIL有可能使ADR诱导的睾丸毒性恶化。
