Effects of Ulinastatin on myocardial oxidative stress and inflammation in severely burned rats

Eur Rev Med Pharmacol Sci. 2018 Sep;22(17):5719-5728. doi: 10.26355/eurrev_201809_15840.

Abstract

Objective: By constructing the severe burns model in rat, we explored the effects of different doses of Ulinastatin (UTI) on protecting myocardium from oxidative stress and inflammatory reaction.

Materials and methods: The severe burns model in rat was first constructed. Burned rats were intervened with different doses of UTI. Contents of cardiac troponin I (cTnI), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in rat serum and heart homogenate were detected by enzyme-linked immunosorbent assay (ELISA). Activities of SOD (superoxide dismutase), CAT (catalase), GSH-Px (glutathione peroxidase), and MDA (malondialdehyde) were detected by commercial kits. The inflammation and pathological changes in rat heart were observed by HE (Hematoxylin-Eosin) staining. Protein expressions of Cox-2, iNOS, NF-κB, Nrf2, and HO-1 in rat myocardium were detected by Western blot.

Results: Higher levels of cTnI, IL-1, IL-6, and TNF-α were found in model group than those of control group (p<0.05). Besides, decreased contents of cTnI, IL-1, IL-6, and TNF-α were observed in both UTI 50 ku/kg group and UTI 100 ku/kg group compared with those of model group (p<0.05). Decreased activities of SOD, CAT, and GSH-Px, as well as increased MDA level were observed in model group than those of control group (p<0.05). However, UTI treatment remarkably elevated SOD, CAT, and GSH-Px activities, whereas downregulated MDA level in burned rats (p<0.05). Abundant infiltration of inflammatory cells was found in the rat's myocardium of model group, which was alleviated in UTI group in a dose-dependent manner. Upregulated Cox-2, iNOS, and NF-κB, as well as downregulated Nrf2 and HO-1 were found in model group compared with those of control group (p<0.05). UTI pretreatment remarkably reversed the above-mentioned trends.

Conclusions: Ulinastatin alleviates myocardial injury induced by severe burns. It exerts a protective role in myocardium via inhibiting oxidative stress and inflammatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Burns / drug therapy*
  • Burns / genetics
  • Burns / metabolism
  • Burns / pathology
  • Cytokines / metabolism*
  • Cytoprotection
  • Disease Models, Animal
  • Gene Expression Regulation
  • Glycoproteins / pharmacology*
  • Inflammation Mediators / metabolism*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Oxidative Stress / drug effects*
  • Rats, Wistar
  • Severity of Illness Index
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Glycoproteins
  • Inflammation Mediators
  • urinastatin