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Inflammation

, Volume 41, Issue 3, pp 803–810 | Cite as

Ulinastatin Protects against CVB3-Induced Acute Viral Myocarditis through Nrf2 Activation

  • Fangqiang Song
  • Fanpo Kong
  • Hongqing Zhang
  • Yongqin Zhou
  • Ming Li
ORIGINAL ARTICLE
  • 110 Downloads

Abstract

Inflammation and oxidative stress are implicated in the pathogenesis of acute viral myocarditis (AVM). Ulinastantin (UTI), an inhibitor of serine protease widely used in treatment of pancreatitis and various inflammatory disorders, displays cardioprotective properties in experimental animals. Although the specific mechanism through which UTI regulates cardiac function is not well explored, evidence suggests that UTI might activate nuclear factor E2-related factor 2 (Nrf2) signaling. In this study, we investigated the role of Nrf2 in mediating UTI’s cardioprotection in a mouse model of AVM. We found that UTI is an activator of Nrf2 signaling. It markedly increased Nrf2 nuclear translocation, Nrf2 transcription capacity, and the downstream protein expression. In addition, UTI possessed strong protective functions in coxsackievirus B3 (CVB3)-induced AVM. UTI treatment effectively reduced the cardiac damage, decreased the expression of inflammatory cytokines, and balanced oxidative stress via improving the activity of anti-oxidant and detoxifying enzymes. Even more impressively, UTI achieved its cardioprotective activities in an Nrf2-dependent manner. Taken together, our study has identified a novel pathway through which UTI exerts its cardioprotective functions and provides a molecular basis for UTI potential applications in the treatment of AVM and other inflammatory disorders.

KEY WORDS

ulinastatin myocarditis inflammation oxidative stress Nrf2 

Abbreviations

AVM

acute viral myocarditis

Nrf2

nuclear factor E2-related factor-2

UTI

ulinastatin

CVB3

coxsackievirus B3

ARE

antioxidant response element

ROS

reactive oxygen species

HO-1

heme oxygenase-1

NQO1

NAD(P)H quinine oxidoreductase 1

LV

left ventricular

EF

end-systolic diameter

FS

fractional shortening

LVEDd

LV diameter at end-diastole

LVESd

LV diameter at end-systole

AST

aspartate amino transferase

LDH

lactate dehydrogenase

CK

creatine kinase

CAT

catalase

SOD

superoxide dismutase

MDA

malonaldehyde

GSH-Px

glutathione peroxidase

TNF-α

tumor necrosis factor-α

IL-6

interleukin-6

IL-1β

interleukin-1β

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Critical Care MedicineTengzhou Central People’s HospitalTengzhouChina
  2. 2.Department of UrologyTengzhou Central People’s HospitalTengzhouChina

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