Premium
Quercetin Attenuates Ethanol‐Induced Iron Uptake and Myocardial Injury by Regulating the Angiotensin II‐L‐Type Calcium Channel
Author(s) -
Guo Xiaoping,
Chen Man,
Zeng Hongmei,
Liu Peiyi,
Zhu Xinghong,
Zhou Feng,
Liu Jingjing,
Zhang Jun,
Dong Zhuangzhuang,
Tang Yuhan,
Gao Chao,
Yao Ping
Publication year - 2018
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201700772
Subject(s) - quercetin , chemistry , calcium channel , calcium , angiotensin ii , ethanol , l type calcium channel , pharmacology , medicine , biochemistry , antioxidant , receptor , organic chemistry
Scope Increased iron deposition in the myocardium in alcoholics may lead to increased risk of cardiac dysfunction. Quercetin has been demonstrated to quench production of intracellular free iron‐induced –OH, but the effect of quercetin in ethanol‐induced cardiac damage remains unclear. This study aims to explore whether quercetin attenuates ethanol‐induced iron uptake and myocardial injury by regulating angiotensin II‐L‐type voltage‐dependent Ca2+ channel (Ang II‐LTCC). Methods and results Adult male C57BL/6J mice are isocalorically pair‐fed either a regular or ethanol‐containing Lieber De Carli liquid diets supplemented with either quercetin (100 mg kg –1 bw) or desferrioxamine mesylate (DFO, 100 mg kg –1 bw) for 15 weeks. Quercetin alleviated ethanol‐induced histopathological changes, creatine kinase isoenzyme release, Ang II secretion, ROS generation, total cardiac iron, and labile iron level. Ethanol exposure or quercetin intervention fails to regulate traditional iron transporters except LTCC. LTCC is upregulated by ethanol and inhibited by quercetin. In H9C2 cell, LTCC is increased by ethanol (100 m m ) and/or Ang II (1 μ m ) concomitant with iron disorders and oxidative stress. This effect is partially normalized by quercetin (50 μ m ), nifedipine (LTCC inhibitor, 15 μ m ), or losartan (Ang II receptor antagonist, 100 μ m ). Conclusion Alcohol‐induced cardiac injury is associated with excessive NTBI uptake mediated by Ang II‐LTCC activation which may be mediated by quercetin against ethanol cardiotoxicity