阿托伐他汀介导的VCAM-1和XO/UA/caspase 3信号下调可避免卵巢缺血/再灌注损伤引起的氧化损伤和细胞凋亡。

IF 5.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Redox Report Pub Date : 2022-12-01 DOI:10.1080/13510002.2022.2129192
O A Afolabi, M A Hamed, D C Anyogu, D H Adeyemi, A F Odetayo, R E Akhigbe
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引用次数: 3

摘要

背景:氧化损伤在卵巢缺血/再灌注(I/R)损伤的发病机制中至关重要,他汀类药物已被报道具有抗氧化活性。然而,VCAM-1和黄嘌呤氧化酶(XO)/尿酸(UA)在卵巢I/R损伤中的作用尚不清楚。此外,阿托伐他汀是否像其他他汀类药物一样具有抗氧化活性尚不清楚。目的:本研究探讨VCAM-1和XO/UA在卵巢I/R损伤中的作用以及阿托伐他汀可能的保护作用。方法:40只雌性Wistar大鼠随机分为假手术组、缺血组、缺血/再灌注组、缺血与阿托伐他汀组、缺血/再灌注组和阿托伐他汀组。结果:与假手术组比较,阿托伐他汀可减轻缺血和I/ r诱导的卵巢组织结构畸变及卵泡变性。此外,阿托伐他汀可减轻缺血和I/ r诱导的XO、UA和丙二醛升高,同时抑制缺血和I/ r诱导的还原性谷胱甘肽水平、酶抗氧化活性、髓过氧化物酶活性和TNF-α、IL-6水平升高。此外,阿托伐他汀阻断了缺血和I/ r诱导的VCAM-1表达、caspase 3活性、8-羟基脱氧鸟苷水平和卵巢DNA片段化指数的升高。结论:本研究首次揭示了阿托伐他汀介导的VCAM-1和XO/UA/caspase 3信号下调可避免卵巢缺血/再灌注损伤引起的氧化损伤、炎症和细胞凋亡。
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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Atorvastatin-mediated downregulation of VCAM-1 and XO/UA/caspase 3 signaling averts oxidative damage and apoptosis induced by ovarian ischaemia/reperfusion injury.

Background: Oxidative damage is critical in the pathogenesis of ovarian ischaemia/reperfusion (I/R) injury, and statins have been reported to exert antioxidant activity. However, the role of VCAM-1 and xanthine oxidase (XO)/uric acid (UA) in ovarian I/R injury is not known. Also, whether or not atorvastatin exerts antioxidant activity like other statins is unclear.

Objectives: This study investigated the involvement of VCAM-1 and XO/UA in ovarian I/R injury and the likely protective role of atorvastatin.

Methods: Forty female Wistar rats were randomized into sham-operated, ischaemia, ischaemia/reperfusion (I/R), ischaemia and atorvastatin, and I/R and atorvastatin.

Results: In comparison with the sham-operated group, atorvastatin blunted ischaemia and I/R-induced distortion of ovarian histoarchitecture and follicular degeneration. Also, atorvastatin alleviated ischaemia and I/R-induced rise in XO, UA, and malondialdehyde, which was accompanied by inhibition of ischaemia and I/R-induced reductions in reduced glutathione level, enzymatic antioxidant activities and increase in myeloperoxidase activity and TNF-α and IL-6 levels by atorvastatin treatment. Additionally, atorvastatin blocked ischaemia and I/R-induced increase in VCAM-1 expression, caspase 3 activity, 8-hydroxydeoxyguanosine level and ovarian DNA fragmentation index.

Conclusion: For the first time, this study revealed that atorvastatin-mediated downregulation of VCAM-1 and XO/UA/caspase 3 signaling averts oxidative injury, inflammation, and apoptosis induced by ovarian ischaemia/reperfusion injury.

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来源期刊
Redox Report
Redox Report 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
28
审稿时长
>12 weeks
期刊介绍: Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.
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