Atorvastatin attenuates the ovarian damage induced by cyclophosphamide in rat: An experimental study|
Hamzeh, Maedeh; Hosseinimehr, Seyed Jalal; Mohammadi, Hamid Reza; Beklar, Saeed Yaghubi; Dashti, Ayat & Amiri, Fereshteh Talebpour
Background: Cyclophosphamide (CP), as an anticancer agent, causes ovarian toxicity and
subsequent infertility in women. Atorvastatin (ATV) at a low dose has antioxidant and antiinflammatory
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
Conclusion: Our results showed that the ATV with antioxidant and anti-apoptosis (caspase-3)
activities protected ovarian against CP-induced toxicity.
Cyclophosphamide; Atorvastatin; Ovary; Oxidative stress; Antioxidant.