Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt.
Hum Exp Toxicol. 2019 Nov;38(11):1283-1295. doi: 10.1177/0960327119865588. Epub 2019 Aug 1.
Cyclophosphamide (CP) causes premature ovarian failure (POF) due to ovarian toxicity. The toxicity mechanism is attributed to oxidative stress, inflammation, and apoptosis. We assessed whether quercetin and rosuvastatin could promote ovarian protection against CP ovotoxicity.
A total of 80 female BALB/c mice were randomly assigned; 10 mice into each of eight groups. Group 1 (control), group 2 (EH), group 3 (CP), group 4 (QH), group 5 (QL), group 6 (RH), group 7 (RL), and group 8 (COM).
Quercetin and rosuvastatin groups (4:8) showed signs of restored ovarian function in the form of a significant, dose-dependent increase in primordial follicles number, serum anti-Mullerian hormone level, and ovarian tissue glutathione level ( < 0.05) versus group 3, and a significant, dose-dependent decrease in atretic follicles number and ovarian tissue level of malondialdehyde ( < 0.05) versus group 3. Immunohistochemistry analysis demonstrated a lower expression of caspase and nuclear factor-kappa B of groups (4:8) versus group 3, although quercetin and rosuvastatin showed a nonsignificant reduction in tumor volume.
We demonstrated the protective effect of quercetin and rosuvastatin against ovarian toxicity and POF induced by CP without compromising its antitumor effect.
环磷酰胺(CP)会导致卵巢毒性,进而引发卵巢早衰(POF)。其毒性机制与氧化应激、炎症和细胞凋亡有关。我们评估了槲皮素和瑞舒伐他汀是否能促进卵巢对 CP 卵巢毒性的保护作用。
共 80 只雌性 BALB/c 小鼠被随机分配;每组 10 只,共 8 组。第 1 组(对照组),第 2 组(EH),第 3 组(CP),第 4 组(QH),第 5 组(QL),第 6 组(RH),第 7 组(RL),第 8 组(COM)。
槲皮素和瑞舒伐他汀组(4:8)表现出卵巢功能恢复的迹象,表现为原始卵泡数量、血清抗苗勒管激素水平和卵巢组织谷胱甘肽水平呈剂量依赖性显著增加(<0.05),与第 3 组相比,闭锁卵泡数量和卵巢组织丙二醛水平呈剂量依赖性显著降低(<0.05)。免疫组织化学分析显示,与第 3 组相比,各剂量组(4:8)的 caspase 和核因子-κB 表达较低,尽管槲皮素和瑞舒伐他汀对肿瘤体积的降低作用不显著。
我们证明了槲皮素和瑞舒伐他汀对 CP 诱导的卵巢毒性和 POF 具有保护作用,而不影响其抗肿瘤作用。