Letras-Luna Dulce Elena, Rosas-Murrieta Nora Hilda, Pazos-Salazar Nidia Gary, Flores-Hernández Jorge, Castelán Francisco, Venegas Berenice, Díaz Alfonso, Treviño Samuel, Juárez-Serrano Daniel, García-Suastegui Wendy Argelia, Handal-Silva Anabella, Morán-Perales José Luis
Department of Biology and Reproductive Toxicology, Institute of Sciences (ICUAP), Benemérita Universidad Autónoma de Puebla, Puebla, Mexico.
Biochemistry and Molecular Biology Laboratory, Chemistry Center, Institute of Sciences (ICUAP), Benemérita Universidad Auténoma de Puebla, Puebla, Mexico.
Int J Endocrinol. 2024 Dec 5;2024:1634072. doi: 10.1155/ije/1634072. eCollection 2024.
In this study, we evaluated the effects of intrabursal administration of cabergoline and N-acetylcysteine on ovarian hyperstimulation syndrome (OHSS) in an immature rat model. The study assessed body, ovarian, and uterine weights, as well as the concentrations of vascular endothelial growth factor A (VEGF-A). Moreover, levels of MDA, 4-HDA, and nitrites were assessed in ovarian homogenates, and vascular permeability was quantified in the peritoneal cavity. Ovarian morphology was characterized using histology and hematoxylin-eosin staining, determining the count of ovarian follicles and corpus luteum. Our results demonstrated a significant increase in lipoperoxidation, nitrite levels, and VEGF-A concentrations in the OHSS group compared to the control group. These biochemical alterations corroborate the successful induction of OHSS in the experimental model. Direct injection into the ovarian bursa resulted in reduced vascular permeability and VEGF-A levels, suggesting that the effects of cabergoline are predominantly ovarian. Particularly, cabergoline did not significantly alter other parameters such as ovarian weight, lipoperoxidation, nitrite levels, or morphology. Conversely, low concentrations of N-acetylcysteine (25-50 µg/kg) significantly reduced ovarian and uterine weights, VEGF-A levels, and vascular permeability. Interestingly, this dose-response relationship was not observed at higher NAC concentrations (100-200 μg/kg), suggesting a potential threshold beyond which NAC loses efficacy in these specific parameters. Our results suggest that the localized administration of N-acetylcysteine shows promise as a therapeutic strategy for OHSS by modulating key parameters associated with the syndrome. These promising results warrant further investigation into its mechanisms and efficacy, potentially expanding therapeutic options for OHSS management.
在本研究中,我们评估了在未成熟大鼠模型中向囊内注射卡麦角林和N-乙酰半胱氨酸对卵巢过度刺激综合征(OHSS)的影响。该研究评估了体重、卵巢和子宫重量,以及血管内皮生长因子A(VEGF-A)的浓度。此外,还评估了卵巢匀浆中丙二醛(MDA)、4-羟基壬烯醛(4-HDA)和亚硝酸盐的水平,并对腹腔内的血管通透性进行了定量分析。使用组织学和苏木精-伊红染色对卵巢形态进行了表征,确定了卵巢卵泡和黄体的数量。我们的结果表明,与对照组相比,OHSS组的脂质过氧化、亚硝酸盐水平和VEGF-A浓度显著增加。这些生化改变证实了实验模型中OHSS的成功诱导。直接注射到卵巢囊中可降低血管通透性和VEGF-A水平,这表明卡麦角林的作用主要在卵巢。特别是,卡麦角林并未显著改变其他参数,如卵巢重量、脂质过氧化、亚硝酸盐水平或形态。相反,低浓度的N-乙酰半胱氨酸(25-50μg/kg)可显著降低卵巢和子宫重量、VEGF-A水平及血管通透性。有趣的是,在较高的N-乙酰半胱氨酸浓度(100-200μg/kg)下未观察到这种剂量反应关系,这表明存在一个潜在阈值,超过该阈值,N-乙酰半胱氨酸在这些特定参数上会失去疗效。我们的结果表明,局部给予N-乙酰半胱氨酸作为一种治疗OHSS的策略,通过调节与该综合征相关的关键参数显示出前景。这些有前景的结果值得进一步研究其机制和疗效,可能会为OHSS的管理拓展治疗选择。