Zinc supplementation prevents cardiomyocyte apoptosis and congenital heart defects in embryos of diabetic mice

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• 作者：Srinivasan Dinesh Kumar ; Murugaiyan Vijaya ; Ramar Perumal Samy ; S. Thameem Dheen ; Minqin Ren ; Frank Watt ; Y. James Kang ; Boon-Huat Bay ; Samuel Sam Wah Tay
• 关键词：EC ; endocardial cushion ; OFT ; outflow tract ; NO ; nitric oxide ; ROS ; reactive oxygen species ; SOD ; superoxide dismutase ; TBARS ; thiobarbituric acid-reactive substance ; MDA ; malondialdehyde ; GPx ; glutathione peroxidase ; GSH ; reduced glutathione ; GSSG ; oxidi
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 出版时间：15 October, 2012
• 年：2012
• 卷：53
• 期：8
• 页码：1595-1606
• 全文大小：1519 K

文摘

Oxidative stress induced by maternal diabetes plays an important role in the development of cardiac malformations. Zinc (Zn) supplementation of animals and humans has been shown to ameliorate oxidative stress induced by diabetic cardiomyopathy. However, the role of Zn in the prevention of oxidative stress induced by diabetic cardiac embryopathy remains unknown. We analyzed the preventive role of Zn in diabetic cardiac embryopathy by both in vivo and in vitro studies. In vivo study revealed a significant decrease in lipid peroxidation, superoxide ions, and oxidized glutathione and an increase in reduced glutathione, nitric oxide, and superoxide dismutase in the developing heart at embryonic days (E) 13.5 and 15.5 in the Zn-supplemented diabetic group when compared to the diabetic group. In addition, significantly down-regulated protein and mRNA expression of metallothionein (MT) in the developing heart of embryos from diabetic group was rescued by Zn supplement. Further, the nuclear microscopy results showed that trace elements such as phosphorus, calcium, and Zn levels were significantly increased (P<0.001), whereas the iron level was significantly decreased (P<0.05) in the developing heart of embryos from the Zn-supplemented diabetic group. In vitro study showed a significant increase in cellular apoptosis and the generation of reactive oxygen species (ROS) in H9c2 (rat embryonic cardiomyoblast) cells exposed to high glucose concentrations. Supplementation with Zn significantly decreased apoptosis and reduced the levels of ROS. In summary, oxidative stress induced by maternal diabetes could play a role in the development and progression of cardiac embryopathy, and Zn supplementation could be a potential therapy for diabetic cardiac embryopathy.