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 a chemotherapy drug, induces hepatotoxicity through causing oxidative stress. Atorvastatin (ATV) at a low dose has antioxidant and anti-inflammatory properties. The present study was designed to investigate the protective effects of ATV against CP-induced hepatotoxicity in rat. In this experimental study, 32 rats were treated with ATV orally at a dose of 10 mg/kg for 10 consecutive days, 5 days before and 5 days after the administration of a single intraperitoneal injection of CP (150 mg/kg). The hepatoprotective effect of ATV was evaluated by measuring liver function markers, oxidative markers, histological and immunohistochemical assays. The biochemical results showed that administration of CP increased hepatic biomarkers enzymes as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels. CP increased malondialdehyde (MDA), protein carbonyl (PC) and decreased glutathione (GSH) content in rats. Moreover, administration of CP was associated with periportal leucocyte infiltration, dilation sinusoids, hepatocyte vacuolation, congestion and hemorrhage in livers of rats. CP significantly increased immunoreactivity of caspase-3 as a marker of apoptosis in liver tissue. ATV markedly mitigated liver injury through reduction in oxidative stress biomarkers, histopathological findings and apoptosis. The antioxidant and anti-apoptotic activities of ATV are main proposed mechanisms involved in its hepatoprotective effects against CP-induced hepatic injury.
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