Dinc Kemal, Ozyurt Ramazan, Coban Taha Abdulkadir, Yazici Gulce Naz, Suleyman Zeynep, Yavuzer Bulent, Suleyman Halis
Department of Obstetrics and Gynecology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey.
Istanbul Women's Health and IVF Center, Istanbul, Turkey.
Taiwan J Obstet Gynecol. 2023 Mar;62(2):256-263. doi: 10.1016/j.tjog.2022.11.011.
In women, agents used in chemotherapy treatment have side effects such as accelerating follicular depletion and early menopause. Thus, cytotoxic treatments may cause various effects ranging from partial damage to the ovary to premature ovarian failure (POI) and infertility. This study aimed to investigate the protective effect of carvacrol on cisplatin (CIS)-induced reproductive toxicity in female rats.
The animals were divided to four groups; a healthy group (HG), administered only cisplatin 2.5 mg/kg (CIS); cisplatin 2.5 mg/kg + carvacrol mg/kg (CC-50), and cisplatin 2.5 mg/kg + carvacrol 100 mg/kg (CC-100). In this study, the CC-50 and CC-100 groups were injected with carvacrol at 50 and 100 mg/kg intraperitoneally (IP). The CIS and HG groupswere administered normal saline as a solvent in the same way. One hour afterwardthe CC-50 and CC-100 groups were injected with cisplatin at 2.5 mg/kg IP. This procedure was continued once a day for 14 days. At the end of this period, six rats from each group were euthanized with high-dose anaesthesia. Biochemical (oxidant-antioxidant and proinflammatory cytokines) and histopathological examinations were performed on the right ovarian tissue removed from the dead rats. The remaining (n = 6 in each group) animals were kept in the laboratory with mature male rats for two months for breeding. Rats that didn't give birth within two months were considered infertile. A one-way ANOVA test was used for the biochemical analysis, the a Kruskal Wallis test was used for the histopathological analysis.
It has been observed that cisplatine causes oxidative stress and inflammatory damage in the ovarian tissue of animals and ultimately causes infertility due to this oxidative stress. While carvacrol significantly suppressed cisplatin-related oxidative stress in ovarian tissue at the 50 and 100 mg/kg doses, it could suppress proinflammatory cytokine increase only at thecytokine increase only at the 100 mg/kg dose. In addition, carvacrol significantly reduced the development of cisplatin-related infertility (from 0 to 83.3%) at a dose of 100 mg/kg.
These findings suggest that carvacrol at high doses can reduce the harmful effects of cisplatin on the ovary and improve ovarian reserve in rats.
在女性中，化疗治疗中使用的药物具有加速卵泡耗竭和过早绝经等副作用。因此，细胞毒性治疗可能会导致从卵巢部分损伤到卵巢早衰（POI）和不孕等各种影响。本研究旨在探讨香芹酚对顺铂（CIS）诱导的雌性大鼠生殖毒性的保护作用。
将动物分为四组；健康组（HG），仅给予顺铂2.5mg/kg（CIS）；顺铂2.5mg/kg + 香芹酚50mg/kg（CC - 50），以及顺铂2.5mg/kg + 香芹酚100mg/kg（CC - 100）。在本研究中，CC - 50组和CC - 100组腹腔注射（IP）50mg/kg和100mg/kg的香芹酚。CIS组和HG组以同样的方式给予生理盐水作为溶剂。一小时后，CC - 50组和CC - 100组腹腔注射2.5mg/kg的顺铂。此程序持续14天，每天一次。在此期间结束时，每组处死6只大鼠，采用高剂量麻醉法。对从处死大鼠取出的右侧卵巢组织进行生化（氧化 - 抗氧化和促炎细胞因子）和组织病理学检查。其余动物（每组n = 6）与成熟雄性大鼠在实验室饲养两个月用于繁殖。两个月内未分娩的大鼠被视为不育。生化分析采用单因素方差分析，组织病理学分析采用Kruskal Wallis检验。
已观察到顺铂会在动物卵巢组织中引起氧化应激和炎症损伤，并最终由于这种氧化应激导致不孕。虽然香芹酚在50mg/kg和100mg/kg剂量时能显著抑制卵巢组织中与顺铂相关的氧化应激，但仅在100mg/kg剂量时能抑制促炎细胞因子的增加。此外，香芹酚在100mg/kg剂量时能显著降低与顺铂相关的不孕发生率（从0降至83.3%）。
这些发现表明，高剂量的香芹酚可以降低顺铂对大鼠卵巢的有害影响，并改善大鼠的卵巢储备。
