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Male infertility is a prominent complication associated with lead exposure, wherein lead has the potential to accumulate within the testes, resulting in oxidative stress and inflammation. In addition, 10-hydroxydecanoic acid (10-HDA) is a component found in the secretions of worker bees and possesses the capacity to mitigate oxidative stress and prevent inflammation. Due to their advantageous properties, zinc oxide nanoparticles (ZnO-NPs) possess a wide range of applications in the field of biomedicine. This study aimed to assess the therapeutic effect of 10-HDA and ZnO-NPs on testicular toxicity in rats induced by lead acetate (PbAc). PbAc was administered orally for a period of 3\u00a0months. Following that, 10-HDA and\/or ZnO-NPs were administrated for 1\u00a0month. PbAc deformed seminal analysis, decreased seminal fructose and sex hormonal levels, and resulted in\u00a0the development of histopathological complications. Additionally, PbAc increased MDA and decreased Nrf2 and HO-1 expression, confirmed by the declined antioxidant defense system. Furthermore, an increase in testicular inflammatory markers and the Bax\/Bcl-2 ratio was observed subsequent to the administration of PbAc. The administration of 10-HDA and ZnO-NPs demonstrated significant efficacy in the restoration of semen quality, pituitary\/gonadal hormones, antioxidants, and \u00a0testicular\u00a0histoarchitecture. Moreover, 10-HDA and ZnO-NPs decreased testicular inflammatory markers and apoptotic proteins (caspase-3 and Bax expression levels). In conclusion, combining 10-HDA and ZnO-NPs demonstrated synergistic potential in treating PbAc-induced testicular toxicity, thereby presenting a promising approach in nanomedicine and natural drugs.<\/jats:p>","DOI":"10.1007\/s12011-024-04374-3","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T22:53:07Z","timestamp":1727736787000},"page":"2728-2751","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["10-Hydroxy Decanoic Acid and Zinc Oxide Nanoparticles Retrieve Nrf2\/HO-1 and Caspase-3\/Bax\/Bcl-2 Signaling in Lead-Induced Testicular Toxicity"],"prefix":"10.1007","volume":"203","author":[{"given":"Adham M.","family":"Maher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghidaa A.","family":"Elsanosy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa A.","family":"Ghareeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar S.","family":"Elblehi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar R.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,30]]},"reference":[{"key":"4374_CR1","doi-asserted-by":"publisher","first-page":"1364352","DOI":"10.3389\/frph.2024.1364352","volume":"6","author":"RJ Aitken","year":"2024","unstructured":"Aitken RJ (2024) What is driving the global decline of human fertility? 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