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

Srinivasan Dinesh Kumar, Murugaiyan Vijaya, Ramar Perumal Samy, S. Thameem Dheen, Minqin Ren, Frank Watt, Yujian Kang, Boon Huat Bay, Samuel Sam Wah Tay

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1595-1606
Number of pages12
JournalFree Radical Biology and Medicine
Volume53
Issue number8
DOIs
StatePublished - Oct 15 2012
Externally publishedYes

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Congenital Heart Defects
Cardiac Myocytes
Zinc
Embryonic Structures
Apoptosis
Defects
Fetal Diseases
Oxidative stress
Oxidative Stress
Medical problems
Nuclear Microscopy
Reactive Oxygen Species
Mothers
Diabetic Cardiomyopathies
Glutathione Disulfide
Metallothionein
Trace Elements
Superoxides
Phosphorus
Lipid Peroxidation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Zinc supplementation prevents cardiomyocyte apoptosis and congenital heart defects in embryos of diabetic mice. / Kumar, Srinivasan Dinesh; Vijaya, Murugaiyan; Samy, Ramar Perumal; Dheen, S. Thameem; Ren, Minqin; Watt, Frank; Kang, Yujian; Bay, Boon Huat; Tay, Samuel Sam Wah.

In: Free Radical Biology and Medicine, Vol. 53, No. 8, 15.10.2012, p. 1595-1606.

Research output: Contribution to journalArticle

Kumar, Srinivasan Dinesh ; Vijaya, Murugaiyan ; Samy, Ramar Perumal ; Dheen, S. Thameem ; Ren, Minqin ; Watt, Frank ; Kang, Yujian ; Bay, Boon Huat ; Tay, Samuel Sam Wah. / Zinc supplementation prevents cardiomyocyte apoptosis and congenital heart defects in embryos of diabetic mice. In: Free Radical Biology and Medicine. 2012 ; Vol. 53, No. 8. pp. 1595-1606.
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AU - Samy, Ramar Perumal

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AU - Ren, Minqin

AU - Watt, Frank

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AU - Bay, Boon Huat

AU - Tay, Samuel Sam Wah

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