L-Citrulline Alleviates Testicular Ischemia/Reperfusion Injury in Rats by Modulating eNOS/iNOS Induced Nitric Oxide Production, Inflammation, and Apoptosis.

IF 1.9 3区 生物学 Q1 ZOOLOGY
Eman M Embaby, Aya Megahed, Sally Abdallah Mostafa, Alaa Samy, Eman H Yousef, Amal F Dawood, Mamdouh Eldesoqui
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引用次数: 0

Abstract

Testicular ischemia/reperfusion injury (TI/RI) is a significant clinical contributor to subfertility and infertility resulting from testicular torsion and subsequent detortion. Insufficient nitric oxide (NO) synthesis in TI/RI can result in endothelial dysfunction, as the vascular endothelium fails to produce sufficient NO to sustain appropriate vasodilation and blood perfusion. Many studies have found that NO plays an important role in the I/RI and its increase or decrease can affect the progression and outcome of I/RI. However, the role of NO in I/RI is controversial and complicated. NO derived by endothelial NO synthase (eNOS) shows a protective role in I/RI, while excessive NO derived by inducible NO synthase (iNOS) accelerates inflammation and increases oxidative stress, further aggravating I/RI. Nevertheless, the overexpression of eNOS may exacerbate I/RI. Here we try to investigate the new progress in the understanding of the roles of NO during I/RI. This study examined the interplay between cytotoxic and cytoprotective mechanisms underpinning NO produced from L-citrulline (L-Cit) on TI/R injured rats. Thirty-two adult Sprague-Dawley albino rats were equally randomized into the following groups: normal control group, sham group, TI/R group (3 h/4 h), and TI/R + L-Cit group (600 mg/kg) orally at 1 h before reperfusion. Compared to the TI/R-operated group, the injection of L-Cit markedly enhanced serum concentrations of reproductive hormones (p < 0.05). Elevated SOD, CAT, and GPx activity, along with reduced MDA and NO concentrations, indicated a diminished oxidative stress. The testicular levels of TNF-α, IL-1β, caspase-3, BAX, eNOS, iNOS, and NF-κB p65 were markedly reduced. Histopathological analysis corroborated the protective effect of L-Cit. The findings confirmed molecular models, demonstrating that L-Cit inhibited eNOS, iNOS, and IKKβ. The results showed that giving torsioned rats NO made from L-Cit protected them against hormonal imbalance, oxidative stress, inflammation, and apoptosis in I/RI. This makes L-Cit even more important for protecting against tissue I/RI during surgery. L-Cit not only promoted NO synthesis through eNOS activation, but it also facilitated the neutralization of iNOS production and its pathogenic NO levels during the reperfusion phase in I/R-injured rats.

通过调节 eNOS/iNOS 诱导的一氧化氮生成、炎症和细胞凋亡缓解大鼠睾丸缺血再灌注损伤
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来源期刊
Journal of experimental zoology. Part A, Ecological and integrative physiology
Journal of experimental zoology. Part A, Ecological and integrative physiology Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
4.90
自引率
3.60%
发文量
0
期刊介绍: The Journal of Experimental Zoology – A publishes articles at the interface between Development, Physiology, Ecology and Evolution. Contributions that help to reveal how molecular, functional and ecological variation relate to one another are particularly welcome. The Journal publishes original research in the form of rapid communications or regular research articles, as well as perspectives and reviews on topics pertaining to the scope of the Journal. Acceptable articles are limited to studies on animals.
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