Cerium oxide nanoparticles protect cyclophosphamide-induced testicular toxicity in mice

Abstract

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 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. 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.

Hidrox® Counteracts Cyclophosphamide-Induced Male Infertility through NRF2 Pathways in a Mouse Model

“…In fact, CYP causes a reduction in the size and number of seminiferous tubules, spermatogonia degeneration and vacuolation, reduced spermatocytes and germ cells, irregular seminiferous tubules, reduced seminiferous epithelial layers, significant maturation arrest, and perivascular fibrosis [ 81 , 103 , 104 ]. The histological structure of CYP-treated mice showed reduction in germinal cells, atrophy in tubules, vacuolization in Sertoli cells, interstitial edema and congestion, and reduced diameters of seminiferous tubules and Johnsen’s Testicular Score [ 64 ]. HD at the dose of 50 mg/kg was able to limit CYP-induced histological alteration.…”

“…injection of CYP (200 mg/kg b.w, i.p.) in distilled water (10 mL/kg b.w) [ 24 , 41 , 64 ]. For the polyphenol treatment, mice received an oral administration of HD at a dose of 50 mg/kg.…”

“…To obtain the sperm, the entire epididymis from the mouse was minced in a sperm-washing medium and incubated for 30 min at room temperature. The sperm parameters were evaluated as previously described in other work [ 64 , 71 ]. The sperm characteristics were determined according to the guidelines of the World Health Organization (WHO) in the WHO Laboratory Manual for the Examination and Processing of Human Semen, 2010.…”

“…Testis were dehydrated, embedded in paraffin, and stained in hematoxylin/eosin (H/E), as previously described [ 72 ]. Investigation of testicular damage was assessed considering Johnsen’s score (JS) system from 0 (No seminiferous epithelial cells; tubular sclerosis) to 10 (Full spermatogenesis) [ 64 , 74 ]. Sections from each mouse were observed using a Leica DM6 microscope (Leica Microsystems SpA, Milan, Italy) and scored in a blinded fashion.…”

“…Numerous reports confirm its value, highlighting HT’s strong antioxidant capacity and potential to destroy free radicals [ 50 , 51 , 52 , 53 ]. Different studies demonstrate its cardioprotective, anticancer, neuroprotective, and antimicrobial effects [ 50 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. Additionally, HT interacts with proteins involved in cell cycle regulation and gene expression and possesses anti-inflammatory, antiatherogenic, and antithrombotic properties [ 58 , 59 , 60 , 61 , 62 ].…”