Cerium Oxide Nanoparticles Protect Cyclophosphamide‑induced Testicular Toxicity in Mice

Maedeh Hamzeh, Seyed Jalal Hosseinimehr, Abbasali Karimpour, Hamid Reza Mohammadi, Ali Reza Khalatbary, Fereshteh Talebpour Amiri


Background: 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.

Methods: 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.

Results: 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
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
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
caspase‑3 immunoreactivity induced by CP in testis.

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

Keywords: Caspase‑3, cerium oxide, cyclophosphamide, oxidative stress, testis, toxicity

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