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 Citations (Scopus)

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

Fingerprint

Aldehyde Reductase
Sepsis
Anti-Inflammatory Agents
Cecum
Punctures
Chemokines
Cytokines
Ligation
Oxidative stress
Oxidative Stress
HMGB Proteins
Systemic Inflammatory Response Syndrome
Ascitic Fluid
Transcription
Endotoxins
Transcriptional Activation
Spleen
Chemical activation
Tissue
Kidney

Keywords

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

ASJC Scopus subject areas

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

Cite this

Anti-inflammatory effect of aldose reductase inhibition in murine polymicrobial sepsis. / Reddy, Aramati B M; Srivastava, Satish; Ramana, Kota.

In: Cytokine, Vol. 48, No. 3, 12.2009, p. 170-176.

Research output: Contribution to journalArticle

Reddy, Aramati B M ; Srivastava, Satish ; Ramana, Kota. / Anti-inflammatory effect of aldose reductase inhibition in murine polymicrobial sepsis. In: Cytokine. 2009 ; Vol. 48, No. 3. pp. 170-176.
@article{ba6e5281c3554aadb699bf3272f06d07,
title = "Anti-inflammatory effect of aldose reductase inhibition in murine polymicrobial sepsis",
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.",
keywords = "Aldose reductase, Cecum ligation and puncture, Cytokines, Inflammation, Sepsis",
author = "Reddy, {Aramati B M} and Satish Srivastava and Kota Ramana",
year = "2009",
month = "12",
doi = "10.1016/j.cyto.2009.07.004",
language = "English (US)",
volume = "48",
pages = "170--176",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Anti-inflammatory effect of aldose reductase inhibition in murine polymicrobial sepsis

AU - Reddy, Aramati B M

AU - Srivastava, Satish

AU - Ramana, Kota

PY - 2009/12

Y1 - 2009/12

N2 - 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.

AB - 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.

KW - Aldose reductase

KW - Cecum ligation and puncture

KW - Cytokines

KW - Inflammation

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=70350023106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350023106&partnerID=8YFLogxK

U2 - 10.1016/j.cyto.2009.07.004

DO - 10.1016/j.cyto.2009.07.004

M3 - Article

VL - 48

SP - 170

EP - 176

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 3

ER -