title: Zinc supplementation prevents cardiomyocyte apoptosis and congenital heart defects in embryos of diabetic mice.
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.
authors: Department of Anatomy, National University Health System, National University of Singapore, Singapore 117597. dineshkumar@ntu.edu.sg
authors: Srinivasan Dinesh
authors: SD
authors: Kumar
authors: Murugaiyan
authors: M
authors: Vijaya
authors: Ramar Perumal
authors: RP
authors: Samy
authors: S Thameem
authors: ST
authors: Dheen
authors: Minqin
authors: M
authors: Ren
authors: Frank
authors: F
authors: Watt
authors: Y James
authors: YJ
authors: Kang
authors: Boon-Huat
authors: BH
authors: Bay
authors: Samuel Sam Wah
authors: SS
authors: Tay
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D019587:Dietary Supplements; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007124:Immunoenzyme Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D062345:Nuclear Microscopy; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D008668:Metallothionein; D013482:Superoxide Dismutase; D005978:Glutathione; D015032:Zinc