Zingerone suppresses liver inflammation induced by antibiotic mediated endotoxemia through down regulating hepatic mRNA expression of inflammatory markers in Pseudomonas aeruginosa peritonitis mouse model

PLoS One. 2014 Sep 3;9(9):e106536. doi: 10.1371/journal.pone.0106536. eCollection 2014.

Abstract

Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale) against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2) indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti-inflammatory phytomedicine against hepatic inflammation induced by antibiotic mediated endotoxemia. These results thus suggest that zingerone treatment can be used as a co-therapy with antibiotics to reduced endotoxin induced inflammation during treatment of severe P.aeruginosa infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Disease Models, Animal
  • Endotoxemia / chemically induced
  • Endotoxemia / complications
  • Endotoxemia / pathology
  • Endotoxins / biosynthesis
  • Endotoxins / toxicity
  • Gene Expression Regulation / drug effects
  • Guaiacol / administration & dosage
  • Guaiacol / analogs & derivatives*
  • Humans
  • Inflammation / chemically induced
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / microbiology
  • Inflammation / pathology
  • Liver / drug effects
  • Liver / microbiology
  • Liver / pathology
  • Mice
  • Peritonitis / genetics*
  • Peritonitis / microbiology
  • Peritonitis / pathology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / pathogenicity
  • RNA, Messenger / biosynthesis

Substances

  • Anti-Bacterial Agents
  • Endotoxins
  • RNA, Messenger
  • zingerone
  • Guaiacol

Grants and funding

The authors acknowledge the financial support by INSPIRE programme of Department of Science and technology (DST) Govt of India in the form of a Senior Research Fellowship to the first author. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.