International Journal of Preventive Medicine (Int J Prev Med)2008-78021012019012320087802ENDepartment of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center & Department of Anatomy, Faculty of Medicine, Student Research Committee, Mazandaran University of Medical Sciences, SariDepartment of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, SariDepartment of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, SariDepartment of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, SariDepartment of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, SariDepartment of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari20190123<p><span class="fontstyle0"><strong>Background</strong>: </span><span class="fontstyle2">Cyclophosphamide (CP), as a chemotherapy drug, causes severe damage in testicular tissue through producing free radicals. Cerium oxide nanoparticles (NC) exhibit antioxidant and anti‑inflammatory properties. The purpose of this study was to investigate the protective effect of NC on CP‑induced testicular damage in mice. </span></p><p><span class="fontstyle0"><strong>Methods</strong>: </span><span class="fontstyle2">In this experimental study, thirty‑two male mice were divided into four groups (eight mice in each group). The control group was received intraperitoneally (IP) normal saline, NC group was received NC for three consecutive days (100 </span><span class="fontstyle3">µ</span><span class="fontstyle2">g/kg, IP), CP group was received CP (200 mg/kg, IP), and the CP + NC group received NC, three consecutive days before receiving CP. After 2 days, testicles were assessed for biochemical, histomorphometrical, histopathological, and immunohistochemical analyses. </span></p><p><strong></strong><span class="fontstyle0"><strong>Results</strong>: </span><span class="fontstyle2">CP administration caused statistically signifcant increases in sperm abnormality, malondialdehyde, protein carbonyl levels, reactive oxygen species, level and apoptosis, and decreases in sperm count, sperm viability, testosterone, glutathione activity, the mean thickness of<br />the germinal epithelium, diameter of seminiferous tubules in mice. Degeneration, necrosis, arrest of spermatogenesis, congestion, and atrophy in testicular tissue confrmed the low Johnsen’s Testicular<br />score in CP group. Administration of NC signifcantly ameliorated the CP‑induced adverse effects on testis compared with the CP group. In addition, pretreatment mice with NC signifcantly reduced<br />caspase‑3 immunoreactivity induced by CP in testis. </span></p><p><strong></strong><span class="fontstyle0"><strong>Conclusions</strong>: </span><span class="fontstyle2">This study showed that NC with scavenging free radicals and antiapoptotic properties enable to reduce the side effects of CP in the<br />testicular tissue.<br /></span></p><p><span class="fontstyle0" style="color: #00652e;"><strong>Keywords</strong>: </span><span class="fontstyle4">Caspase‑3, cerium oxide, cyclophosphamide, oxidative stress, testis, toxicity</span></p>http://ijpm.mui.ac.ir/index.php/ijpm/article/view/1992http://ijpm.mui.ac.ir/index.php/ijpm/article/download/1992/717717812