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催产素改善脂多糖诱导的急性睾丸炎模型:氧化应激与炎症途径的相互作用

Oxytocin ameliorates lipopolysaccharide-induced acute orchitis model: interplay of oxidative stress and inflammatory pathways.

作者信息

El-Sherbiny Mohamed, Elkattawy Hany A, Hadhoud Shimaa, Nasr Ahmed N, Ibrahim Ateya M, Ameer Omar Z, Alsaleebi Noorhan, Asfari Joud, Zakari Madaniah O, Mojaddidi Moaz A, Ali Ehab K, Almohaimeed Hailah M, Abdeen Ahmed, Ali Sahar K, Eldesoqui Mamdouh

机构信息

Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia.

Department of Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

出版信息

Front Pharmacol. 2025 Jan 7;15:1506777. doi: 10.3389/fphar.2024.1506777. eCollection 2024.

Abstract

INTRODUCTION

Lipopolysaccharide (LPS), a constituent of the outer membrane of Gram-negative bacteria, is a powerful inducer of systemic inflammation and has been extensively utilized in experimental models to simulate inflammatory responses and septic disorders. Recent research indicates that oxytocin (OXY), a neuropeptide typically linked to social bonding and reproductive functions, may influence inflammatory processes. This work examines the impact of OXY on LPS-induced testicular damage, aiming to elucidate its therapeutic potential in addressing inflammatory disorders and broadening the comprehension of its functions beyond conventional neuroendocrine roles.

METHODS

Eighteen male albino rats were divided into three groups; the control group received no treatment; the LPS group received 0.5 mL of saline solution containing 5 mg/kg LPS intraperitoneally (orchitis model); and the LPS + OXY group received LPS and OXY (0.1 mg/kg) intraperitoneally every 12 h for 72 h.

RESULTS AND DISCUSSION

Animals subjected to LPS were found to have severe orchitis, as evidenced by increased oxidative stress and surging inflammatory mediators (TNF-α, IL-1β, and IL-6), with declined IL-10 levels. Besides, LPS increased the malondialdehyde (MDA) and decreased the glutathione (GSH) levels, inducing an oxidative stress cascade. In addition, there are dramatic increases in the TLR4, MyD88, NF-κB, and PK2/PKR1 protein expression levels. All these events could alter the sperm count, morphology, and testicular architecture.

CONCLUSION

Interestingly, OXY could mitigate LPS-induced oxidative damage and inflammation in testicular tissue alongside restoring the disrupted sperm count, motility, and morphology. This therapeutic potential of OXY might be accounted for by its anti-inflammatory, antioxidant, and antiapoptotic activities.

摘要

引言

脂多糖(LPS)是革兰氏阴性菌外膜的一种成分,是全身炎症的强力诱导剂,已被广泛用于实验模型中以模拟炎症反应和脓毒症。最近的研究表明,催产素(OXY),一种通常与社会联系和生殖功能相关的神经肽,可能影响炎症过程。这项工作研究了OXY对LPS诱导的睾丸损伤的影响,旨在阐明其在解决炎症性疾病方面的治疗潜力,并拓宽对其超越传统神经内分泌作用的功能的理解。

方法

18只雄性白化大鼠分为三组;对照组不接受治疗;LPS组腹腔注射0.5 mL含5 mg/kg LPS的盐溶液(睾丸炎模型);LPS + OXY组每12小时腹腔注射LPS和OXY(0.1 mg/kg),持续72小时。

结果与讨论

接受LPS处理的动物出现严重睾丸炎,氧化应激增加和炎症介质(TNF-α、IL-1β和IL-6)激增,IL-10水平下降证明了这一点。此外,LPS增加了丙二醛(MDA)水平,降低了谷胱甘肽(GSH)水平,引发了氧化应激级联反应。此外,TLR4、MyD88、NF-κB和PK2/PKR1蛋白表达水平显著增加。所有这些事件都可能改变精子数量、形态和睾丸结构。

结论

有趣的是,OXY可以减轻LPS诱导的睾丸组织氧化损伤和炎症,同时恢复受干扰的精子数量、活力和形态。OXY的这种治疗潜力可能归因于其抗炎、抗氧化和抗凋亡活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ba8/11752902/cfd00b912883/fphar-15-1506777-g001.jpg

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