College of Animal Science and Technology, Northwest A&F University, Xianyang 712100, China.
College of Forestry, Northwest A&F University, Xianyang 712100, China.
Int J Mol Sci. 2024 Jun 7;25(12):6320. doi: 10.3390/ijms25126320.
Busulfan, an indispensable medicine in cancer treatment, can cause serious reproductive system damage to males as a side effect of its otherwise excellent therapeutic results. Its widespread use has also caused its accumulation in the environment and subsequent ecotoxicology effects. As a Chinese medicine, Wulingzhi (WLZ) has the effects of promoting blood circulation and improving female reproductive function. However, the potential effects of WLZ in male reproduction and in counteracting busulfan-induced testis damage, as well as its probable mechanisms, are still ambiguous. In this study, busulfan was introduced in a mouse model to evaluate its production of the testicular damage. The components of different WLZ extracts were compared using an untargeted metabolome to select extracts with greater efficacy, which were further confirmed in vivo. Here, we demonstrate abnormal spermatogenesis and low sperm quality in busulfan-injured testes. The WLZ extracts showed a strong potential to rehabilitate the male reproductive system; this effect was more prominent in room-temperature extracts. Additionally, both water and ethanol WLZ extracts at room temperature alleviated various busulfan-induced adverse effects. In particular, WLZ recovered spermatogenesis, re-activated arginine biosynthesis, and alleviated the increased oxidative stress and inflammation in the testis, ultimately reversing the busulfan-induced testicular injury. Collectively, these results suggest a promising approach to protecting the male reproductive system from busulfan-induced adverse side effects, as well as those of other similar anti-cancer drugs.
白消安是癌症治疗中不可或缺的药物，但它也有一个严重的副作用，会对男性的生殖系统造成损害。由于其治疗效果出色，因此被广泛使用，这也导致其在环境中积累，并产生了生态毒理学效应。作为一种中药，五指灵芝（WLZ）具有促进血液循环和改善女性生殖功能的作用。然而，WLZ 在男性生殖中的潜在作用，以及其对抗白消安引起的睾丸损伤的作用机制，仍不明确。在本研究中，我们在小鼠模型中引入了白消安，以评估其对睾丸损伤的产生作用。通过非靶向代谢组学比较了不同 WLZ 提取物的成分，以选择具有更大疗效的提取物，并在体内进一步验证。结果表明，白消安损伤的睾丸出现了异常的精子发生和精子质量下降。WLZ 提取物具有很强的恢复男性生殖系统的潜力；这种作用在室温提取物中更为明显。此外，水和乙醇室温 WLZ 提取物均能缓解白消安引起的各种不良反应。特别是，WLZ 恢复了精子发生，重新激活了精氨酸生物合成，并减轻了睾丸中增加的氧化应激和炎症，最终逆转了白消安引起的睾丸损伤。综上所述，这些结果表明，WLZ 可能是一种有前途的方法，可以保护男性生殖系统免受白消安引起的不良副作用，以及其他类似抗癌药物的副作用。
