关键词: Apoptosis Cyclophosphamide Dexpanthenol POF Reproductive toxicology

Mesh : Animals Female Cyclophosphamide / toxicity adverse effects Pantothenic Acid / analogs & derivatives pharmacology Rats, Wistar Ovary / drug effects pathology Primary Ovarian Insufficiency / chemically induced Rats Ovarian Follicle / drug effects Oxidative Stress / drug effects Apoptosis / drug effects Proliferating Cell Nuclear Antigen / metabolism Follicle Stimulating Hormone / blood TOR Serine-Threonine Kinases / metabolism Anti-Mullerian Hormone / blood

来  源:   DOI:10.1016/j.rbmo.2023.103778

Abstract:
OBJECTIVE: Does dexpanthenol work as an effective therapeutic agent against cyclophosphamide (CYC)-induced premature ovarian failure (POF) in rats?
METHODS: A total of 28 female Wistar Albino rats were randomly divided into four groups (n = 7 per group). The POF and POF plus dexpanthenol groups were intraperitoneally administered CYC at an initial dose of 50 mg/kg, followed by 8 mg/kg for 14 days. The dexpanthenol and POF plus dexpanthenol groups were both intraperitoneally administered dexpanthenol at a dose of 500 mg/kg/day for 15 days.
RESULTS: In the group administered CYC, the following was observed: a decrease in the ovarian index; a decrease in the numbers of primordial, primary, secondary and antral follicles; an increase in the number of corpus luteum and atretic follicles; a decrease in proliferation cell nuclear antigen immunoreactivity; a significant reduction in anti-Müllerian hormone and oestradiol levels; and an increase in serum FSH levels compared with controls. Dexpanthenol, on the other hand, reversed these effects. Quantitative reverse transcription polymerase chain reaction analyses showed that dexpanthenol increased Bcl-2, Akt1, mTOR, Nrf2 and HO-1 in CYC-induced ovarian tissues, but decreased Bax, Cas3, Hsp27, Hsp70, and Hsp90. Dexpanthenol treatment has a potential for inhibiting the intrinsic apoptotic pathway and oxidative stress levels in ovarian tissues via the downregulation of the mRNA expression of heat shock proteins and the activation of Nrf2/HO-1 pathways.
CONCLUSIONS: Our findings demonstrated that dexpanthenol is an effective agent against POF caused by CYC; however, further experimental and clinical data are needed to use it effectively.
摘要:
目的:右泛醇是否可以有效治疗环磷酰胺(CYC)诱导的大鼠卵巢早衰(POF)?
方法:将28只雌性Wistar白化病大鼠随机分为四组(每组7只)。POF和POF加右泛醇组腹膜内施用CYC,初始剂量为50mg/kg,8mg/kg,持续14天。右泛醇和POF加右泛醇组均以500mg/kg/天的剂量腹膜内施用右泛醇15天。
结果:在给予CYC的组中,观察到以下情况:卵巢指数下降;原始数量减少,小学,次级和窦卵泡;黄体和闭锁卵泡数量增加;增殖细胞核抗原免疫反应性降低;抗苗勒管激素和雌二醇水平显着降低;与对照组相比,血清FSH水平升高。Dexpanthenol,另一方面,扭转了这些影响。定量逆转录聚合酶链反应分析表明,右泛醇增加Bcl-2,Akt1,mTOR,Nrf2和HO-1在CYC诱导的卵巢组织中,但减少了Bax,Cas3、Hsp27、Hsp70和Hsp90。右泛醇治疗具有通过下调热休克蛋白的mRNA表达和激活Nrf2/HO-1途径来抑制卵巢组织中内在凋亡途径和氧化应激水平的潜力。
结论:我们的研究结果表明,右泛醇是抗CYC引起的POF的有效药物;然而,需要进一步的实验和临床数据来有效使用它。
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