Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits
BackgroundThere are several mechanisms, including inflammation, oxidative stress and abnormal calcium homeostasis, involved in the pathogenesis of atrial fibrillation. In diabetes mellitus (DM), increased oxidative stress may be attributable to higher xanthine oxidase activity. In this study, we exa...
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2018
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oai:doaj.org-article:b2b24cc82df244e7b6ca0289aaa87abc2021-11-12T17:01:59ZXanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits10.1161/JAHA.118.0088072047-9980https://doaj.org/article/b2b24cc82df244e7b6ca0289aaa87abc2018-05-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.118.008807https://doaj.org/toc/2047-9980BackgroundThere are several mechanisms, including inflammation, oxidative stress and abnormal calcium homeostasis, involved in the pathogenesis of atrial fibrillation. In diabetes mellitus (DM), increased oxidative stress may be attributable to higher xanthine oxidase activity. In this study, we examined the relationship between oxidative stress and atrial electrical and structural remodeling, and calcium handling abnormalities, and the potential beneficial effects of the xanthine oxidase inhibitor allopurinol upon these pathological changes. Methods and ResultsNinety rabbits were randomly and equally divided into 3 groups: control, DM, and allopurinol‐treated DM group. Echocardiographic and hemodynamic assessments were performed in vivo. Serum and tissue markers of oxidative stress and atrial fibrosis, including the protein expression were examined. Atrial interstitial fibrosis was evaluated by Masson trichrome staining. ICaL was measured from isolated left atrial cardiomyocytes using voltage‐clamp techniques. Confocal microscopy was used to detect intracellular calcium transients. The Ca2+ handling protein expression was analyzed by Western blotting. Mitochondrial‐related proteins were analyzed as markers of mitochondrial function. Compared with the control group, rabbits with DM showed left ventricular hypertrophy, increased atrial interstitial fibrosis, oxidative stress and fibrosis markers, ICaL and intracellular calcium transient, and atrial fibrillation inducibility. These abnormalities were alleviated by allopurinol treatment. ConclusionsAllopurinol, via its antioxidant effects, reduces atrial mechanical, structural, ion channel remodeling and mitochondrial synthesis abnormalities induced by DM‐related increases in oxidative stress.Yajuan YangJianping ZhaoJiuchun QiuJian LiXue LiangZhiwei ZhangXiaowei ZhangHuaying FuPanagiotis KorantzopoulosKonstantinos P. LetsasGary TseGuangping LiTong LiuWileyarticleallopurinolatrial fibrillationcalcium signalingDiabetes mellitusmitochondriaoxidative stressDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 7, Iss 10 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
allopurinol atrial fibrillation calcium signaling Diabetes mellitus mitochondria oxidative stress Diseases of the circulatory (Cardiovascular) system RC666-701 |
| spellingShingle |
allopurinol atrial fibrillation calcium signaling Diabetes mellitus mitochondria oxidative stress Diseases of the circulatory (Cardiovascular) system RC666-701 Yajuan Yang Jianping Zhao Jiuchun Qiu Jian Li Xue Liang Zhiwei Zhang Xiaowei Zhang Huaying Fu Panagiotis Korantzopoulos Konstantinos P. Letsas Gary Tse Guangping Li Tong Liu Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits |
| description |
BackgroundThere are several mechanisms, including inflammation, oxidative stress and abnormal calcium homeostasis, involved in the pathogenesis of atrial fibrillation. In diabetes mellitus (DM), increased oxidative stress may be attributable to higher xanthine oxidase activity. In this study, we examined the relationship between oxidative stress and atrial electrical and structural remodeling, and calcium handling abnormalities, and the potential beneficial effects of the xanthine oxidase inhibitor allopurinol upon these pathological changes. Methods and ResultsNinety rabbits were randomly and equally divided into 3 groups: control, DM, and allopurinol‐treated DM group. Echocardiographic and hemodynamic assessments were performed in vivo. Serum and tissue markers of oxidative stress and atrial fibrosis, including the protein expression were examined. Atrial interstitial fibrosis was evaluated by Masson trichrome staining. ICaL was measured from isolated left atrial cardiomyocytes using voltage‐clamp techniques. Confocal microscopy was used to detect intracellular calcium transients. The Ca2+ handling protein expression was analyzed by Western blotting. Mitochondrial‐related proteins were analyzed as markers of mitochondrial function. Compared with the control group, rabbits with DM showed left ventricular hypertrophy, increased atrial interstitial fibrosis, oxidative stress and fibrosis markers, ICaL and intracellular calcium transient, and atrial fibrillation inducibility. These abnormalities were alleviated by allopurinol treatment. ConclusionsAllopurinol, via its antioxidant effects, reduces atrial mechanical, structural, ion channel remodeling and mitochondrial synthesis abnormalities induced by DM‐related increases in oxidative stress. |
| format |
article |
| author |
Yajuan Yang Jianping Zhao Jiuchun Qiu Jian Li Xue Liang Zhiwei Zhang Xiaowei Zhang Huaying Fu Panagiotis Korantzopoulos Konstantinos P. Letsas Gary Tse Guangping Li Tong Liu |
| author_facet |
Yajuan Yang Jianping Zhao Jiuchun Qiu Jian Li Xue Liang Zhiwei Zhang Xiaowei Zhang Huaying Fu Panagiotis Korantzopoulos Konstantinos P. Letsas Gary Tse Guangping Li Tong Liu |
| author_sort |
Yajuan Yang |
| title |
Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits |
| title_short |
Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits |
| title_full |
Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits |
| title_fullStr |
Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits |
| title_full_unstemmed |
Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits |
| title_sort |
xanthine oxidase inhibitor allopurinol prevents oxidative stress‐mediated atrial remodeling in alloxan‐induced diabetes mellitus rabbits |
| publisher |
Wiley |
| publishDate |
2018 |
| url |
https://doaj.org/article/b2b24cc82df244e7b6ca0289aaa87abc |
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