Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1.

IF 1.1 Q2 MEDICINE, GENERAL & INTERNAL

Medeniyet medical journal Pub Date : 2024-12-27 DOI:10.4274/MMJ.galenos.2024.04932

Kübra Tuğçe Kalkan, Betül Yalçın, Özge Cengiz Mat, Arzu Hanım Yay

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引用次数: 0

Abstract

Objective: Methotrexate (MTX) is a highly effective chemotherapy for cancer. This drug has a gonadotoxic effect, mainly in the testes and ovaries. Our study used histopathological and immunohistochemical methods to assess the potential damage to testicular and ovarian tissue caused by MTX use.

Methods: Twenty-four Wistar albino rats, both male and female, were used in our study. Four sets of rats; control male, MTX male, control female, and MTX female were created. The male and female MTX-treated groups received a single intraperitoneal dose of 20 mg/kg MTX. The testes and ovaries of rats sacrificed under general anesthesia were extracted and histopathologically analyzed. In addition, the immunoreactivity intensities of stem cell factor (SCF), mechanistic target of rapamycin (mTOR), and SIRT-1 in both tissues were measured by immunohistochemistry.

Results: Johnsen's testicular biopsy score in the testicular seminiferous tubules was significantly lower in the MTX group than in the control group (p<0.001). The ovary showed substantial follicular degeneration (p<0.05), vascular congestion (p<0.01), and fibrosis (p<0.001). MTX reduced SCF immunoreactivity density in the testis and ovary (p<0.05). Furthermore, MTX reduced mTOR, a marker of autophagy, in the testis (p<0.05) and ovary (p<0.001) compared with the control. SIRT-1 intensity increased dramatically in the testis (p<0.001) and ovary (p<0.01) in the injured group, unlike the mTOR marker.

Conclusions: Our investigation revealed that the gonads incurred significant damage as a result of MTX. One vital option for reducing or eliminating this damage to the ovaries and testicles is the use of anti-oxidant-rich substances.

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甲氨蝶呤诱导的大鼠性腺损伤的组织病理学和免疫组织化学评价：SCF、mTOR和SIRT-1的作用。

目的：甲氨蝶呤（MTX）是一种高效的肿瘤化疗药物。这种药物有促性腺毒性作用，主要作用于睾丸和卵巢。本研究采用组织病理学和免疫组织化学方法评估使用甲氨蝶呤对睾丸和卵巢组织的潜在损害。方法：选用Wistar白化大鼠24只，雌雄各1只。四组大鼠；对照雄性、MTX雄性、对照雌性和MTX雌性被创建。雄性和雌性甲氨蝶呤治疗组给予单次腹腔注射剂量20 mg/kg甲氨蝶呤。取全麻处死大鼠的睾丸和卵巢，进行组织病理学分析。此外，通过免疫组织化学检测两种组织中干细胞因子（SCF）、雷帕霉素（mTOR）和SIRT-1的免疫反应性强度。结果：MTX组睾丸精小管的Johnsen睾丸活检评分明显低于对照组(结论：我们的研究显示，MTX对性腺造成了显著的损害。减少或消除对卵巢和睾丸的损害的一个重要选择是使用富含抗氧化剂的物质。

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

Medeniyet medical journal Medicine-Medicine (all)

CiteScore

1.70

自引率

0.00%

发文量

审稿时长

5 weeks

期刊介绍： The Medeniyet Medical Journal (Medeniyet Med J) is an open access, peer-reviewed, and scientific journal of Istanbul Medeniyet University Faculty of Medicine on various academic disciplines in medicine, which is published in English four times a year, in March, June, September, and December by a group of academics. Medeniyet Medical Journal is the continuation of Göztepe Medical Journal (ISSN: 1300-526X) which was started publishing in 1985. It changed the name as Medeniyet Medical Journal in 2015. Submission and publication are free of charge. No fees are asked from the authors for evaluation or publication process. All published articles are available online in the journal website (www.medeniyetmedicaljournal.org) without any fee. The journal publishes intradisciplinary or interdisciplinary clinical, experimental, and basic researches as well as original case reports, reviews, invited reviews, or letters to the editor, Being published since 1985, the Medeniyet Med J recognizes that the best science should lead to better lives based on the fact that the medicine should serve to the needs of society, and knowledge should transform society. The journal aims to address current issues at both national and international levels, start debates, and exert an influence on decision-makers all over the world by integrating science in everyday life. Medeniyet Med J is committed to serve the public and influence people’s lives in a positive way by making science widely accessible. Believing that the only goal is improving lives, and research has an impact on people’s lives, we select the best research papers in line with this goal.