Protection by dimethyl fumarate against diabetic cardiomyopathy in type 1 diabetic mice likely via activation of nuclear factor erythroid-2 related factor 2

Xinyue Hu, Mohanraj Rajesh, Jian Zhang, Shanshan Zhou, Shudong Wang, Jian Sun, Yi Tan, Yang Zheng, Lu Cai

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Oxidative stress and inflammation play key roles in the development of diabetic cardiomyopathy (DCM). Dimethyl fumarate (DMF), an FDA approved medicine for relapsing multiple sclerosis, has manifested its antioxidant and anti-inflammatory function mostly in the central nervous system. In this study, we investigated whether DMF could attenuate the development of DCM. Type 1 diabetes mouse model was established using multiple low-dose streptozotocin, and the diabetic mice were treated with DMF (10 mg/kg body weight) for 3 months. Cardiac functions were determined using echocardiography. Oxidative stress, pro-inflammatory cytokines and pro-fibrotic markers were determined with commercially available kits, real-time quantitative PCR or western blot techniques. DCM was characterized by diminished cardiac function, accompanied by oxidative stress and enhanced expression of pro-inflammatory cytokines. Diabetic cardiac tissue exhibited marked fibrosis, revealed by extracellular matrix deposition as determined by Sirius red staining of the myocardial tissues. Furthermore, Nrf2 and its downstream effectors were repressed in diabetic myocardium. On the contrary, diabetic animals treated with DMF exhibited blunted oxidative stress, inflammation, fibrosis and this correlated with Nrf2 activation. Our findings suggest that DMF could potentially thwart diabetes-induced myocardial tissue injury, likely via activation of Nrf2 function, providing firm impetus for future repurposing of DMF in the management of DCM.

Original languageEnglish
Pages (from-to)131-141
Number of pages11
JournalToxicology Letters
Volume287
DOIs
Publication statusPublished - May 1 2018

Keywords

  • Diabetes
  • Dimethyl fumarate
  • Nuclear factor erythroid-2 related factor 2 (Nrf2)
  • Oxidative stress

ASJC Scopus subject areas

  • Toxicology

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