Quercetin reduces oxidative stress and inhibits activation of c‑Jun N‑terminal kinase/activator protein‑1 signaling in an experimental mouse model of abdominal aortic aneurysm

Wang,Lian; Cheng,Xiaofeng; Li,Hao; Qiu,Fang; Yang,Nan; Wang,Bo; Lu,Huchen; Wu,Haiwei; Shen,Yi; Wang,Yanqing; Jing,Hua

doi:10.3892/mmr.2013.1846

Quercetin reduces oxidative stress and inhibits activation of c‑Jun N‑terminal kinase/activator protein‑1 signaling in an experimental mouse model of abdominal aortic aneurysm

Authors:
- Lian Wang
- Xiaofeng Cheng
- Hao Li
- Fang Qiu
- Nan Yang
- Bo Wang
- Huchen Lu
- Haiwei Wu
- Yi Shen
- Yanqing Wang
- Hua Jing
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Affiliations: Department of Thoracic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Jiangsu 210009, P.R. China, D.A. Diagnostic Laboratory, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, Jiangsu 210009, P.R. China, Department of Neurological Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, Jiangsu 210009, P.R. China, Department of Cardiology, The 81st Hospital of PLA, Nanjing, Jiangsu 210002, P.R. China
Published online on: December 6, 2013 https://doi.org/10.3892/mmr.2013.1846
Pages: 435-442
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Oxidative stress is becoming increasingly linked to the pathogenesis of abdominal aortic aneurysms (AAAs). The antioxidant activity of flavonoids has attracted attention for their possible role in the prevention of cardiovascular diseases. The purpose of this study was to determine whether an antioxidant mechanism is involved in the aneurysm formation inhibitory effect afforded by quercetin. Male C57/BL6 mice received quercetin continuously from 2 weeks prior to and 6 weeks following the AAA induction with extraluminal CaCl2. Quercetin treatment decreased AAA incidence and inhibited the reactive oxygen species generation, nitrotyrosine formation and lipid peroxidation production in the aortic tissue during AAA development. In addition, quercetin‑treated mice exhibited significantly lower expression of the p47phox subunit of nicotinamide adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase, as well as coordinated downregulation of manganese‑superoxide dismutase activities and glutathione peroxidase (GPx)‑1 and GPx‑3 expression. Quercetin also blunted the expression of c‑Jun N‑terminal kinase (JNK) and phospho‑JNK and, in addition, diminished activation of the activator protein (AP)‑1 transcription factor. Gelatin zymography showed that quercetin eliminated matrix metalloproteinase (MMP)‑2 and MMP‑9 activation during AAA formation. In conclusion, the inhibitory effects of quercetin on oxidative stress and MMP activation, through modulation of JNK/AP‑1 signaling, may partly account for its benefit in CaCl2‑induced AAA.

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