Department of Histology and Cell Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt.
Department Anatomy, College of Medicine, Umm Al-Qura University, Mecca, KSA.
J Histotechnol. 2023 Jun;46(2):65-79. doi: 10.1080/01478885.2022.2105481. Epub 2022 Aug 1.
Limited literature was available on the effects of sitagliptin or quercetin treatments on doxorubicin induced ovarian dysfunction in diabetic animals. The study aim was test the efficacy and suggested mechanisms of quercetin/sitagliptin combined treatment on the doxorubicin-induced ovarian toxicity in rat model with streptozotocin-induced diabetes. Forty eight female Wistar rats were divided into six groups: 1) Control; 2) Streptozotocin induced diabetes; 3) Streptozotocin-induced diabetes + doxorubicin ovarian damage; 4) Streptozotocin-induced diabetes + doxorubicin ovarian damage with; 5) Streptozotocin-induced diabetes + doxorubicin ovarian damage with sitagliptin treatment and 6) Streptozotocin-induced diabetes + doxorubicin ovarian damage with concomitant quercetin/sitagliptin treatment. Biochemical tests for serum estrogen, progesterone, insulin, blood glucose, and ovarian levels of malondialdehyde, nitric oxide, and superoxide dismutase and qRT-PCR for NOBOX, FSHr, and iNOS genes were performed. Histological evaluation was done on ovary sections with hematoxylin and eosin and immunohistochemistry for 8-OHdG and iNOS followed by morphometric analysis. The streptozotocin-induced diabetic group showed varying degrees of follicle atresia and altered biochemical parameters, both were marked in the streptozotocin-induced diabetic + doxorubicin group. The mRNA of NOBOX, FSHr, and iNOS genes were disturbed with increased immunoexpression of iNOS and 8-OHdG. Quercetin and/or sitagliptin administration improved all altered histological and biochemical parameters and was more effective as a combined treatment. The study suggested equal efficacy of both quercetin and sitagliptin in mitigating the doxorubicin-induced ovarian toxicity in the streptozotocin diabetic rat model, and the combined therapy showed anti-inflammatory, anti-antioxidant, and anti-DNA damage mechanisms.
关于西他列汀或槲皮素治疗对糖尿病动物多柔比星诱导的卵巢功能障碍的影响，文献资料有限。本研究旨在测试槲皮素/西他列汀联合治疗对链脲佐菌素诱导糖尿病大鼠模型中多柔比星诱导的卵巢毒性的疗效及其可能的机制。将 48 只雌性 Wistar 大鼠分为六组：1）对照组；2）链脲佐菌素诱导的糖尿病；3）链脲佐菌素诱导的糖尿病+多柔比星卵巢损伤；4）链脲佐菌素诱导的糖尿病+多柔比星卵巢损伤+西他列汀治疗；5）链脲佐菌素诱导的糖尿病+多柔比星卵巢损伤+槲皮素/西他列汀联合治疗；6）链脲佐菌素诱导的糖尿病+多柔比星卵巢损伤+槲皮素/西他列汀联合治疗。对血清雌激素、孕激素、胰岛素、血糖以及卵巢丙二醛、一氧化氮和超氧化物歧化酶水平进行生化检测，并用 qRT-PCR 检测 NOBOX、FSHr 和 iNOS 基因。对卵巢组织进行苏木精-伊红染色和 8-OHdG 和 iNOS 的免疫组织化学染色，并进行形态计量学分析。链脲佐菌素诱导的糖尿病组表现出不同程度的卵泡闭锁和生化参数改变，链脲佐菌素诱导的糖尿病+多柔比星组更为明显。NOBOX、FSHr 和 iNOS 基因的 mRNA 受到干扰，iNOS 和 8-OHdG 的免疫表达增加。槲皮素和/或西他列汀给药改善了所有改变的组织学和生化参数，联合治疗更为有效。研究表明，槲皮素和西他列汀在减轻链脲佐菌素糖尿病大鼠模型中多柔比星诱导的卵巢毒性方面具有同等疗效，联合治疗具有抗炎、抗氧化和抗 DNA 损伤机制。
