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Int J Prev Med. 2019 Jan 15;10:5. doi: 10.4103/ijpvm.IJPVM_184_18. eCollection 2019.

Cerium Oxide Nanoparticles Protect Cyclophosphamide-induced Testicular Toxicity in Mice.

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Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Anatomy, Faculty of Medicine, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.



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.


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 μg/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.


CP administration caused statistically significant 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 the germinal epithelium, diameter of seminiferous tubules in mice. Degeneration, necrosis, arrest of spermatogenesis, congestion, and atrophy in testicular tissue confirmed the low Johnsen's Testicular score in CP group. Administration of NC significantly ameliorated the CP-induced adverse effects on testis compared with the CP group. In addition, pretreatment mice with NC significantly reduced caspase-3 immunoreactivity induced by CP in testis.


This study showed that NC with scavenging free radicals and antiapoptotic properties enable to reduce the side effects of CP in the testicular tissue.


Caspase-3; cerium oxide; cyclophosphamide; oxidative stress; testis; toxicity

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