Catechin hydrate alleviates tramadol-induced ovarian and uterine injury through regulation of oxidative and ER stress, apoptosis, steroidogenesis, and hormonal imbalance

IF 3.4 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2026-03-01 Epub Date: 2025-12-04 DOI:10.1016/j.reprotox.2025.109132

Ramazan Bülbül , Hasan Şimşek , Nurhan Akaras , Özge Kandemir , Fatih Mehmet Kandemir , Cüneyt Çağlayan , Aydın Genç

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引用次数: 0

Abstract

Aim

This study investigated the harmful effects of tramadol (TRD) exposure on ovarian and uterine tissue, with a specific focus on oxidative stress and the damage pathways it triggers. It also aimed to establish whether catechin hydrate (CTH), a potent antioxidant flavonoid, could protect against or repair TRD-induced reproductive toxicity.

Methods

28 Wistar rats were randomly divided into four groups: Control, CTH, TRD, and TRD+CTH. TRD (50 mg/kg, intraperitoneal) and CTH (20 mg/kg, oral) were administered daily for a period of 14 days. Subsequent to the administration of treatment, blood, ovarian, and uterine tissues were collected for biochemical, qRT-PCR, histopathological, and immunohistochemical analyses to evaluate oxidative and ER stress, inflammation and apoptotic damage, hormonal changes, and tissue damage.

Results

TRD administration significantly increased oxidative stress (MDA, p < 0.001), inflammation (NF-κB, TNF-α, IL-1β, p < 0.001), apoptosis (Caspase-3, Bax, p < 0.001), and ER stress (PERK, ATF6, p < 0.001), while suppressing antioxidant parameters, Bcl-2 and steroidogenic enzyme expression (CYP11A1, CYP17A1, CYP19A1, p < 0.001) and reducing serum AMH, E2, FSH, and LH levels (p < 0.001). Co-administration of CTH markedly reversed these effects by restoring antioxidant and hormonal balance (p < 0.05–0.001) and downregulating oxidative, inflammatory, and apoptotic markers. Histologically, CTH treatment notably improved TRD-induced ovarian and uterine degeneration, reducing inflammation, congestion, and follicular atresia while preserving tissue integrity (p < 0.05).

Conclusion

The findings of this study suggest that CTH may offer protective effects against TRD-induced ovarian and uterine toxicity by mitigating oxidative stress, inflammation, apoptosis, and ER stress, thereby supporting hormonal balance and tissue integrity.

查看原文本刊更多论文

儿茶素通过调节氧化应激、内质网络应激、细胞凋亡、甾体生成和激素失衡，减轻曲马多诱导的卵巢和子宫损伤。

目的：本研究探讨曲马多（TRD）暴露对卵巢和子宫组织的有害影响，特别关注氧化应激及其引发的损伤途径。儿茶素水合物（CTH）是一种有效的抗氧化剂类黄酮，它是否能预防或修复trd诱导的生殖毒性。方法：28只Wistar大鼠随机分为对照组、CTH组、TRD组、TRD+CTH组。每日给予TRD （50mg/kg，腹腔注射）和CTH （20mg/kg，口服），连续14天。在给药后，收集血液、卵巢和子宫组织进行生化、qRT-PCR、组织病理学和免疫组织化学分析，以评估氧化和内质网应激、炎症和凋亡损伤、激素变化和组织损伤。结论：本研究结果提示CTH可能通过减轻氧化应激、炎症、细胞凋亡和内质网应激，从而支持激素平衡和组织完整性，对TRD诱导的卵巢和子宫毒性具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.