Comparative efficacy of melatonin and glutathione in mitigating carboplatin-induced ovarian toxicity in rats

IF 2.4 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics Pub Date : 2026-01-01 Epub Date: 2026-03-12 DOI:10.1016/j.clinsp.2026.100902

Halime Tozak Yıldız , Kübra Tuğçe Kalkan , Özge Cengiz Mat , Eda Köseoğlu , Özge Göktepe , Gözde Özge Önder , Arzu Yay

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引用次数: 0

Abstract

Objective

This study aimed to compare the comparative protective effects of Melatonin (Mel) and Glutathione (GSH) against Carboplatin (CARB)-induced ovarian toxicity in rats, with a focus on folliculogenesis, oxidative stress, inflammation, and apoptosis.

Methods

Female Wistar rats were allocated into six groups: Control, GSH, Mel, CARB, GSH+CARB, and Mel+CARB. Mel and GSH were administered intraperitoneally for 7 days before CARB injection. Ovarian tissues were subjected to histopathological and morphometric analyses, while serum oxidative stress markers (MDA, SOD, CAT, GSH-Px), proinflammatory cytokines (TNF-α, IL-6), and AMH levels were quantified. Caspase-3 and NF-κB expressions were evaluated immunohistochemically.

Results

CARB caused severe ovarian injury characterized by marked follicular depletion, stromal edema, hemorrhage, inflammation, fibrosis, and a significant reduction in preantral and Graafian follicles, with a concomitant increase in atretic follicles (p < 0.01). Both Mel and GSH pre-treatment markedly reduced histological damage, restored follicular counts, improved antioxidant status, and suppressed inflammatory and apoptotic responses. Melatonin tended to exert stronger protective effects on certain parameters, particularly in preserving AMH levels, attenuating fibrosis, and reducing Caspase-3 and NF-κB expression, although the differences between Mel+CARB and GSH+CARB groups were not statistically significant in all comparisons.

Conclusion

Pre-treatment with melatonin or glutathione effectively mitigated CARB-induced ovarian toxicity by modulating oxidative stress, inflammation, and apoptosis. Melatonin appeared to provide relatively greater protection in some parameters, but without consistent statistical superiority over glutathione. These results underscore the potential of antioxidant-based strategies for fertility preservation during chemotherapy. Further studies with larger sample sizes and direct comparative analyses are warranted to clarify relative efficacy and confirm translational relevance.

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褪黑素和谷胱甘肽减轻卡铂所致大鼠卵巢毒性的比较疗效

本研究旨在比较褪黑素（Mel）和谷胱甘肽（GSH）对卡铂（CARB）诱导的大鼠卵巢毒性的保护作用，重点关注卵泡发生、氧化应激、炎症和细胞凋亡。方法雌性Wistar大鼠分为对照组、GSH组、Mel组、CARB组、GSH+CARB组和Mel+CARB组。Mel和GSH在CARB注射前腹腔注射7天。对卵巢组织进行组织病理学和形态计量学分析，同时定量测定血清氧化应激标志物（MDA、SOD、CAT、GSH-Px）、促炎因子（TNF-α、IL-6）和AMH水平。免疫组织化学法检测Caspase-3和NF-κB的表达。结果scarb可引起严重的卵巢损伤，其特征是卵泡明显减少、间质水肿、出血、炎症、纤维化，且腔前卵泡和Graafian卵泡明显减少，同时闭锁卵泡增加（p < 0.01）。Mel和GSH预处理均可显著减少组织损伤，恢复卵泡计数，改善抗氧化状态，抑制炎症和凋亡反应。褪黑素对某些参数具有更强的保护作用，特别是在保持AMH水平、减轻纤维化、降低Caspase-3和NF-κB表达方面，尽管Mel+CARB组与GSH+CARB组之间的差异在所有比较中均无统计学意义。结论褪黑素或谷胱甘肽预处理可通过调节氧化应激、炎症和细胞凋亡，有效减轻carb诱导的卵巢毒性。褪黑素似乎在某些参数上提供了相对更大的保护，但在统计上没有谷胱甘肽的一致性优势。这些结果强调了化疗期间以抗氧化剂为基础的生育保护策略的潜力。进一步的研究需要更大的样本量和直接的比较分析来澄清相对疗效和确认翻译相关性。

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

Clinics 医学-医学：内科

CiteScore

4.10

自引率

3.70%

发文量

129

审稿时长

52 days

期刊介绍： CLINICS is an electronic journal that publishes peer-reviewed articles in continuous flow, of interest to clinicians and researchers in the medical sciences. CLINICS complies with the policies of funding agencies which request or require deposition of the published articles that they fund into publicly available databases. CLINICS supports the position of the International Committee of Medical Journal Editors (ICMJE) on trial registration.