Moradi Saman, Khazaei Mozafar, Rashidi Zahra
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Cell J. 2023 Jul 25;25(7):496-507. doi: 10.22074/cellj.2023.1989732.1234.
Premature ovarian failure (POF) is a heterogeneous disorder. POF is defined as hypergonadotropic hypoestrogenism in women under 40 years. There is no effective treatment to cure POF patients. Antioxidants prevent ovarian damage by reducing the lipid peroxidation cascades affecting folliculogenesis, meiosis and ovulation. Hence; the aim of present study was to investigate the effects of Capsaicin (CAP) and Quercetin (QUR) on cyclophosphamide (CYC)-induced POF in rat model.
In this experimental study, POF was induced by intraperitoneal injection of 200 mg/kg CYC on first day and then 8 mg/kg/day for the following 3 days. After 4 days of CYC administration, rats were randomly divided into five groups (n=6/group) as follows: POF, dimethyl sulfoxide (DMSO), CAP (0.5 mg/kg/day), QUR (100 mg/kg/day) and CAP+QUR. Biochemical, hormonal, gene expression, and histological evaluations were performed on blood serum and tissue samples after 14 days of treatment with the CAP and QUR.
CAP, QUR and CAP+QUR groups showed signs of restored ovarian function in the form of a significant increase in serum total antioxidant capacity (TAC), estrogen, progesterone and anti-mullerian hormone (AMH) levels versus POF and DMSO groups and a significant improvement in histological parameters and follicle numbers in treatment groups compared to POF and DMSO groups. Polymerase chain reaction (PCR) analysis demonstrated that CAP and QUR upregulate the expression of BAX gene and decreased the expression of apoptosis inducing genes (BCL-2 and P53).
CAP and QUR treatment of CYC-induced POF rats showed a positive effect on reducing ovarian damage by improving TAC levels, expression of apoptotic genes, levels of ovarian reserve markers, and histological parameters. Our results suggest that treatment with CAP or QUR may be a conservative treatment approach for CYC -induced POF.
卵巢早衰(POF)是一种异质性疾病。POF被定义为40岁以下女性的高促性腺激素性低雌激素血症。目前尚无治愈POF患者的有效治疗方法。抗氧化剂通过减少影响卵泡发生、减数分裂和排卵的脂质过氧化级联反应来预防卵巢损伤。因此,本研究的目的是探讨辣椒素(CAP)和槲皮素(QUR)对环磷酰胺(CYC)诱导的大鼠POF模型的影响。
在本实验研究中,第一天腹腔注射200mg/kg CYC诱导POF,随后3天每天注射8mg/kg。CYC给药4天后,将大鼠随机分为五组(每组n = 6):POF组、二甲基亚砜(DMSO)组、CAP(0.5mg/kg/天)组、QUR(100mg/kg/天)组和CAP + QUR组。在用CAP和QUR治疗14天后,对血清和组织样本进行生化、激素、基因表达和组织学评估。
与POF组和DMSO组相比,CAP组、QUR组和CAP + QUR组表现出卵巢功能恢复的迹象,血清总抗氧化能力(TAC)、雌激素、孕酮和抗苗勒管激素(AMH)水平显著升高,并且与POF组和DMSO组相比,治疗组的组织学参数和卵泡数量有显著改善。聚合酶链反应(PCR)分析表明,CAP和QUR上调BAX基因的表达并降低凋亡诱导基因(BCL-2和P53)的表达。
CAP和QUR治疗CYC诱导的POF大鼠通过提高TAC水平、凋亡基因表达、卵巢储备标志物水平和组织学参数,对减少卵巢损伤显示出积极作用。我们的结果表明,CAP或QUR治疗可能是CYC诱导的POF的一种保守治疗方法。