Effect of Betaine on Apoptosis and Oxidative Stress in Methotrexate-Induced Testicular Damage in Mice

IF 2.1 4区 医学 Q3 ANDROLOGY Andrologia Pub Date : 2024-11-22 DOI:10.1155/and/4126428
Fatemeh Rezaei-Tazangi, Negar Varaa, Zahra Kazemikia, Arash Goodarzi, Layasadat Khorsandi
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Abstract

Background: Methotrexate (MTX) is widely administered to manage various cancers. However, MTX induces spermatogenic defects.

Objective: This study investigated the protective effects of betaine (BET) against MTX–induced testicular damage.

Materials and Methods: Forty-eight male mice were randomly divided into six groups: control, BET (300 mg/kg), MTX (20 mg/kg), and MTX (20 mg/kg) + BET (100, 200, and 300 mg/kg) groups. Testosterone levels, histological changes, sperm quality, apoptosis, and oxidative stress biomarkers were assessed to evaluate the protective effects of BET.

Results: MTX disrupted germinal epithelium, reduced sperm quality, and decreased serum testosterone levels, as well as induced apoptosis and oxidative stress in the testicular tissue. BET dose dependently restored the testosterone levels and catalase (CAT) and superoxide dismutase (SOD). Furthermore, BET reduced lipid peroxidation, as indicated by decreased malondialdehyde (MDA) levels. BET preserved normal spermatogenesis, improved sperm quality, and reduced histological changes by MTX. Moreover, BET reduced apoptosis by decreasing the Bcl-2 Associated X-protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio in the testicular tissue of the MTX-intoxicated mice.

Conclusion: The results indicate that BET mitigates testicular harm triggered by MTX by inhibiting apoptosis and decreasing oxidative stress levels.

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甜菜碱对甲氨蝶呤诱导的小鼠睾丸损伤中细胞凋亡和氧化应激的影响
背景:甲氨蝶呤(MTX)被广泛用于治疗各种癌症。然而,MTX 会诱发生精缺陷。 研究目的本研究探讨甜菜碱(BET)对 MTX 引起的睾丸损伤的保护作用。 材料与方法:将 48 只雄性小鼠随机分为 6 组:对照组、BET(300 毫克/千克)组、MTX(20 毫克/千克)组、MTX(20 毫克/千克)+ BET(100、200 和 300 毫克/千克)组。对睾酮水平、组织学变化、精子质量、细胞凋亡和氧化应激生物标志物进行评估,以评价 BET 的保护作用。 结果显示MTX破坏了生精上皮,降低了精子质量,降低了血清睾酮水平,并诱导了睾丸组织中的细胞凋亡和氧化应激。BET 可依赖性地恢复睾酮水平、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)。此外,BET 还能减少脂质过氧化反应,丙二醛(MDA)水平的降低就说明了这一点。BET 可保持正常的精子发生,改善精子质量,并减少 MTX 造成的组织学变化。此外,BET 还能降低 MTX 中毒小鼠睾丸组织中的 Bcl-2 相关 X 蛋白(Bax)/B 细胞淋巴瘤 2(Bcl-2)比率,从而减少细胞凋亡。 结论研究结果表明,BET可通过抑制细胞凋亡和降低氧化应激水平来减轻MTX对睾丸的伤害。
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来源期刊
Andrologia
Andrologia 医学-男科学
CiteScore
5.60
自引率
8.30%
发文量
292
审稿时长
6 months
期刊介绍: Andrologia provides an international forum for original papers on the current clinical, morphological, biochemical, and experimental status of organic male infertility and sexual disorders in men. The articles inform on the whole process of advances in andrology (including the aging male), from fundamental research to therapeutic developments worldwide. First published in 1969 and the first international journal of andrology, it is a well established journal in this expanding area of reproductive medicine.
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