Anti-inflammatory effect of aldose reductase inhibition in murine polymicrobial sepsis

Aramati B M Reddy, Satish Srivastava, Kota Ramana

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Aim: Increased production of cytokines and chemokines in serum and tissues upon oxidative stress caused by severe systemic infections are the major cause of sepsis. Aldose reductase (AR) known to mediate oxidative stress-induced NF-κB activation and transcription of cytokines and chemokines are the main mediator of bacterial endotoxin-induced inflammatory response. Our aim is to investigate the effect of AR inhibitors on the prevention of inflammatory cytokines in the cecum ligation and puncture (CLP) model of polymicrobial sepsis which closely mimics the sepsis syndrome in humans. Results: Mice were rendered septic by CLP in the absence and presence of AR inhibitor, sorbinil. The levels of cytokines, chemokines and other inflammatory markers in the plasma, peritoneal fluid and heart of mice were significantly inhibited by sorbinil. Inhibition of AR also prevented CLP-induced COX-2, iNOS and HMGB-1 in heart, kidney and spleen. Conclusions: Our results showed that the inhibition of AR significantly prevented the polymicrobial sepsis-induced increase in inflammatory markers and thus indicate the use of AR inhibitors as anti-inflammatory agents.

Original languageEnglish (US)
Pages (from-to)170-176
Number of pages7
JournalCytokine
Volume48
Issue number3
DOIs
StatePublished - Dec 2009

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Keywords

  • Aldose reductase
  • Cecum ligation and puncture
  • Cytokines
  • Inflammation
  • Sepsis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

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