Background:Cyclophosphamide (CP), as an anticancer agent, causes ovarian toxicity and subsequent infertility in women. Atorvastatin (ATV) at a low dose has antioxidant and anti-inflammatory properties.Objective:The aim of this study was to investigate the protective effect of ATV against CP-induced ovarian injury in rat.Materials and Methods:In this experimental study, thirty-two female Wistar rats were randomly divided into four groups as I) control, II) ATV (10 mg/kg), III) CP (150 mg/kg), and IV) CP +ATV. The ATV treated groups were received ATV for 10 days via oral gavage. In the CP+ATV group, ATV was administrated on 5 days before and 5 days after CP injection. Histological structure, apoptosis (caspase-3), oxidative stress parameters as malondialdehyde, reactive oxygen species, protein carbonyl levels and cell viability were evaluated in ovary tissue by histological scores, immunohistochemistry, histochemical and biochemical assays. The levels of estrogen and progesterone hormones were measured on the 12th day of study.Results:ATV pretreatment significantly decreased the levels of oxidative stress biomarkers as malondialdehyde, reactive oxygen species and protein carbonyl levels and increased cell death in CP-treated rats as compared with the CP alone group. ATV significantly increased estrogen and progesterone levels in CP-treated rats. In addition, the histological examination showed ATV mitigated acute inflammation, degenerative cells in stroma and follicles, stromal edema, vacuolization, atresia of the follicles and congestion of blood vessels in the CP-treated animals. Furthermore, ATV significantly reduced immunoreactivity level of caspase-3 in CP-treated rats.Conclusion:Our results showed that the ATV with antioxidant and anti-apoptosis (caspase-3) activities protected ovarian against CP-induced toxicity.

Cyclophosphamide [CP], as alkylating agents has side effects such as nephrotoxicity. Cerium oxide nanoparticles [nanoceria; NC], as an antioxidant, are effective at reduction oxidative stress. This study evaluated the protective effect of nanoceria in nephrotoxicity induced CP. 32 BALB/c mice were randomly divided into four equal groups. Control, NC, CP and NC+CP. NC and CP injected intraperitoneally respectively in dose of 100 μg/kg for 3 days and 200 mg/kg single dose on 3th day of study. Two days after the final treatment, histochemical, serum biochemical, histopathological and immunohistochemical examinations were performed for determination effects of NC on nephrotoxicity. Oxidative stress and renal injury induced in CP treated mice were proved by the significantly elevation of urea and creatinine and alteration in oxidative stress markers [MDA and GSH levels]. Consequently, histopathological changes and apoptosis were markedly increased. NC was able to reduce MDA, urea , creatinine and increase GSH content. In addition, NC pretreatment could alleviated immunoreactivity of caspase-3. NC revealed a strong antioxidant in nephrotoxicity following CP treatment. This study suggests that NC through antioxidant and antiapoptotic properties have protective effect against CP-induced nephrotoxicity.

Objective: Cyclophosphamide (CP), as an anticancer agent has side effects, especially hepatotoxicity. Cerium oxide nanoparticles [nanoceria (NC)], which act as antioxidants, have a protective effect against oxidative stress-induced toxicity. This study evaluated the preventive effect of NC in hepatotoxicity induced by CP. Materials and Methods: Thirty-two mice were randomly distributed into four groups: control (received only normal saline), NC (received NC 100 μg/kg for 3 days, intraperitoneally), CP (received CP 200 mg/kg single dose on the third day of the study, intraperitoneally), and NC+CP (NC 100 μg/kg and CP 200 mg/kg). Two days after the final treatment, oxidative stress marker (MDA and GSH) and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels were measured, and histopathological and immunohistochemical examinations were performed for determining the effects of NC on hepatotoxicity. Results: CP-induced hepatotoxicity was evident by the significant elevation of liver enzyme levels and alteration in oxidative stress marker levels. Additionally, histopathological changes and apoptosis were markedly increased. NC decreased MDA level, increased GSH level and decreased liver enzyme levels in CP-treated mice. In addition, NC pretreatment could be alleviated by the immunoreactivity of caspase-3 in CP-treated mice compared with the CP group. Conclusion: NC showed a potent antioxidant effect in hepatotoxicity induced by CP. The study suggested that NC through its antioxidant and anti-apoptotic properties has a protective effect against hepatotoxicity induced by CP.

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