Abstract
Cardiac malformations are frequently observed in infants born of diabetic mothers in the clinics. Metallothionein (MT) is a cysteine‐rich protein that binds metals such as zinc (Zn) and acts as an antioxidant that is very efficient in scavenging various free radicals or reactive oxygen species (ROS). We analyzed the preventive role of Zn in diabetic cardiac embryopathy. In vivo study revealed a significant decrease in lipid peroxidation, superoxide ions, oxidized glutathione and an increase in reduced glutathione, nitric oxide and superoxide dismutase in the developing heart at E13.5 and E15.5 in Zn supplemented diabetic group when compared to diabetic group. In addition, significantly down‐regulated protein and mRNA expression of MT in the developing heart of embryos from the diabetic group was rescued by Zn supplementation. Further, 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 ROS in H9c2 cells exposed to high glucose concentrations. Supplementation with Zn significantly decreased apoptosis and reduced the levels of ROS. In summary, 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.Grant Funding Source: Academic Research Fund Singapore & Start‐Up Grant, LKCMedicine
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