Xiaoping Guo1,2,3, Man Chen4, Hongmei Zeng1,2,3, Peiyi Liu1,2,3, Xinghong Zhu1,2,3, Feng Zhou1,2,3, Jingjing Liu1,2,3, Jun Zhang1, Zhuangzhuang Dong1, Yuhan Tang1,2,3, Chao Gao5, Ping Yao1,2,3. 1. Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 3. Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. Wuhan Centers for Disease Prevention and Control, Wuhan, China. 5. National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China.
Abstract
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 mm) and/or Ang II (1 μm) concomitant with iron disorders and oxidative stress. This effect is partially normalized by quercetin (50 μm), nifedipine (LTCC inhibitor, 15 μm), or losartan (Ang II receptor antagonist, 100 μm). 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.
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 mm) and/or Ang II (1 μm) concomitant with iron disorders and oxidative stress. This effect is partially normalized by quercetin (50 μm), nifedipine (LTCC inhibitor, 15 μm), or losartan (Ang II receptor antagonist, 100 μm). CONCLUSION:Alcohol-induced cardiac injury is associated with excessive NTBI uptake mediated by Ang II-LTCC activation which may be mediated by quercetin against ethanolcardiotoxicity.
Authors: Abu Shufian Ishtiaq Ahmed; Matilda H C Sheng; Kin-Hing William Lau; Sean M Wilson; M Daniel Wongworawat; Xiaolei Tang; Mahdis Ghahramanpouri; Antoine Nehme; Yi Xu; Amir Abdipour; Xiao-Bing Zhang; Samiksha Wasnik; David J Baylink Journal: Am J Physiol Cell Physiol Date: 2022-04-06 Impact factor: 5.282