Pseudoephedrine Nanoparticles Alleviate Adriamycin-Induced Reproductive Toxicity Through the GnRhR Signaling Pathway

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.