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伪麻黄碱纳米粒通过 GnRhR 信号通路减轻阿霉素诱导的生殖毒性
Authors Fu Y , Yuan P, Zheng Y, Wei Y, Gao L, Ruan Y , Chen Y, Li P, Feng W, Zheng X
Received 25 November 2021
Accepted for publication 11 March 2022
Published 1 April 2022 Volume 2022:17 Pages 1549—1566
DOI https://doi.org/10.2147/IJN.S348673
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Phong A Tran
Purpose: Pseudoephedrine (PSE) has rapid absorption and metabolism, which limits its pharmacologic actions. We postulated that pseudoephedrine nanoparticles (PSE-NPs) with high bioavailability could overcome this limitation. The defensive function of PSE-NPs nanoparticles against adriamycin-induced reproductive toxicity in mice was studied.
Methods: We encapsulated PSE in polylactide-polyglycolide nanoparticles (PLGA-NPs) and verified their protective activity against testicular injury in vivo and in vitro.
Results: We report a promising delivery system that loads PSE into PLGA-NPs and finally assembles it into a nanocomposite particle. In vitro, PSE-NPs reduced the adriamycin-induced apoptosis of GC-1 cells significantly, improved mitochondrial energy metabolism and promoted expression of the proteins related to the gonadotropin-releasing hormone (GnRh) receptor signaling pathway. In vivo, evaluation of sperm indices and histology showed that adriamycin could induce testicular toxicity. PSE-NPs significantly increased the sperm motility of mice, reduced the percent apoptosis and oxidative stress of testes, increased serum levels of GnRh, activated the GnRhR signaling pathway in testes and promoted expression of meiosis-related factors.
Conclusion: In view of their safety and efficiency, these PSE-NPs have potential applications in alleviating adriamycin-induced reproductive toxicity.
Keywords: pseudoephedrine nanoparticles, adriamycin, reproductive toxicity, GnRhR signaling pathway, sperm meiosis