Protection against diabetic cardiomyopathy is achieved using a combination of sulforaphane and zinc in type 1 diabetic OVE26 mice.

Abstract

Sulforaphane (SFN) can effectively induce nuclear factor E2-related factor 2 (Nrf2), and zinc (Zn) can effectively induce metallothionein (MT), both of which have been shown to protect against diabetic cardiomyopathy (DCM). However, it is unclear whether combined treatment with SFN and Zn offers better cardiac protection than either one alone. Here, we treated 5-week-old OVE mice that spontaneously develop type 1 diabetes with SFN and/or Zn for 18 weeks. Cardiac dysfunction, by echocardiography, and pathological alterations and remodelling, shown by cardiac hypertrophy, fibrosis, inflammation and oxidative damage, examined by histopathology, Western blotting and real-time PCR, were observed in OVE mice. All these dysfunction and pathological abnormalities seen in OVE mice were attenuated in OVE mice with treatment of either SFN, Zn or SFN/Zn, and the combined treatment with SFN/Zn was better than single treatments at ameliorating DCM. In addition, combined SFN and Zn treatment increased Nrf2 function and MT expression in the heart of OVE mice to a greater extent than SFN or Zn alone. This indicates that the dual activation of Nrf2 and MT by combined treatment with SFN and Zn may be more effective than monotherapy at preventing the development of DCM via complementary, additive mechanisms.

• Authors: Jiqun Wang, Shudong Wang, Wanning Wang, Jing Chen, Zhiguo Zhang, Qi Zheng, Quan Liu, Lu Cai
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 9 Pg. 6319-6330 (09 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 31270951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Cardiotonic Agents
• Isothiocyanates
• NF-E2-Related Factor 2
• Sulfoxides
• sulforaphane
• Zinc

Topics

• Animals
• Cardiotonic Agents (pharmacology)
• Diabetes Mellitus, Experimental (drug therapy)
• Diabetes Mellitus, Type 1 (drug therapy)
• Diabetic Cardiomyopathies (prevention & control)
• Female
• Heart (drug effects)
• Isothiocyanates (pharmacology)
• Mice
• Mice, Transgenic
• NF-E2-Related Factor 2 (metabolism)
• Oxidation-Reduction (drug effects)
• Oxidative Stress (drug effects)
• Signal Transduction (drug effects)
• Sulfoxides
• Zinc (pharmacology)