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姜黄素纳米晶体减轻环磷酰胺诱导的小鼠睾丸毒性。

Curcumin nanocrystals attenuate cyclophosphamide-induced testicular toxicity in mice.

机构信息

Division of Clinical Embryology, Department of Reproductive Science, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India.

Division of Reproductive Biology, Department of Reproductive Science, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India.

出版信息

Toxicol Appl Pharmacol. 2021 Dec 15;433:115772. doi: 10.1016/j.taap.2021.115772. Epub 2021 Oct 27.

DOI:10.1016/j.taap.2021.115772
PMID:34715073
Abstract

The cancer therapy using cyclophosphamide (CP) has been associated with adverse effects on the testicular function that raises concerns about the future fertility potential among cancer survivors. Curcumin, a polyphenol, has shown to possess a plethora of biological functions including tissue protective effects. In the present study, we investigated the protective effects of curcumin nanocrystals (NC) in mitigation of CP-induced testicular toxicity. Healthy adult (8-10 week) and prepubertal (2 week) male Swiss albino mice were injected with a single dose of CP (200 mg/kg) intraperitoneally (i.p). NC (4 mg/kg, i.p.) was administered every alternate day, for 35 days in adult mice while, a single dose of NC was injected intraperitoneally to prepubertal mice 1 h prior to CP. Administration of multiple doses of NC ameliorated CP-induced testicular toxicity in adult mice, which was evident from the improved sperm functional competence, sperm chromatin condensation, seminiferous tubule architecture and decreased apoptosis in testicular cells. Further, administration of NC 1 h prior to CP in prepubertal mice modulated the expression of genes pertaining to proliferation, pluripotency, DNA damage and DNA repair in spermatogonial cells at 24 h after the treatment. Overall, these results suggest that NC could be a promising chemoprotective agent, which can have potential application in male fertility preservation.

摘要

环磷酰胺(CP)的癌症疗法与睾丸功能的不良反应有关,这引起了人们对癌症幸存者未来生育潜力的关注。姜黄素是一种多酚,具有多种生物学功能,包括组织保护作用。在本研究中,我们研究了姜黄素纳米晶体(NC)在减轻 CP 诱导的睾丸毒性中的保护作用。健康成年(8-10 周)和未成熟(2 周)雄性瑞士白化病小鼠经腹腔内(i.p.)注射单次 CP(200mg/kg)。NC(4mg/kg,i.p.)每隔一天给药一次,成年小鼠给药 35 天,而未成熟小鼠在 CP 前 1 小时腹腔内注射单次剂量的 NC。多次给予 NC 可改善成年小鼠的 CP 诱导的睾丸毒性,这从改善精子功能、精子染色质浓缩、生精小管结构和减少睾丸细胞凋亡中明显看出。此外,在 CP 治疗后 24 小时,在未成熟小鼠中,NC 在 CP 之前 1 小时给药可调节与精原细胞增殖、多能性、DNA 损伤和 DNA 修复相关的基因的表达。总的来说,这些结果表明 NC 可能是一种有前途的化学保护剂,具有男性生育力保护的潜在应用。

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