A potential therapeutic role for aldose reductase inhibitors in the treatment of endotoxin-related inflammatory diseases

Saumya Pandey, Satish Srivastava, Kota Ramana

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Introduction: Aldose reductase (AR) was initially thought to be involved in the secondary diabetic complications because of its glucose-reducing potential. However, evidence from recent studies indicates that AR is an excellent reducer of a number of lipid peroxidation-derived aldehydes as well as their glutathione conjugates, which regulate inflammatory signals initiated by oxidants such as cytokines, growth factors and bacterial endotoxins, and revealed the potential use of AR inhibition as an approach to prevent inflammatory complications. Areas covered: An extensive Internet and Medline search was performed to retrieve information on understanding the role of AR inhibition in the pathophysiology of endotoxin-mediated inflammatory disorders. Overall, inhibition of AR appears to be a promising strategy for the treatment of endotoxemia, sepsis and other related inflammatory diseases. Expert opinion: Current knowledge provides enough evidence to indicate that AR inhibition is a logical therapeutic strategy for the treatment of endotoxin-related inflammatory diseases. Since AR inhibitors have already gone to Phase III clinical studies for diabetic complications and found to be safe for human use, their use in endotoxin-related inflammatory diseases could be expedited. However, one of the major challenges will be the discovery of AR-regulated clinically relevant biomarkers to identify susceptible individuals at risk of developing inflammatory diseases, thereby warranting future research in this area.

Original languageEnglish (US)
Pages (from-to)329-339
Number of pages11
JournalExpert Opinion on Investigational Drugs
Volume21
Issue number3
DOIs
StatePublished - Mar 2012

Fingerprint

Aldehyde Reductase
Endotoxins
Diabetes Complications
Therapeutics
Endotoxemia
Expert Testimony
Oxidants
Aldehydes
Internet
Lipid Peroxidation
Glutathione
Sepsis
Intercellular Signaling Peptides and Proteins
Biomarkers
Cytokines
Glucose

Keywords

  • Aldose reductase
  • Endotoxin
  • Inflammation
  • Sepsis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

A potential therapeutic role for aldose reductase inhibitors in the treatment of endotoxin-related inflammatory diseases. / Pandey, Saumya; Srivastava, Satish; Ramana, Kota.

In: Expert Opinion on Investigational Drugs, Vol. 21, No. 3, 03.2012, p. 329-339.

Research output: Contribution to journalArticle

@article{be4313f26e564df4a29c04aa65392532,
title = "A potential therapeutic role for aldose reductase inhibitors in the treatment of endotoxin-related inflammatory diseases",
abstract = "Introduction: Aldose reductase (AR) was initially thought to be involved in the secondary diabetic complications because of its glucose-reducing potential. However, evidence from recent studies indicates that AR is an excellent reducer of a number of lipid peroxidation-derived aldehydes as well as their glutathione conjugates, which regulate inflammatory signals initiated by oxidants such as cytokines, growth factors and bacterial endotoxins, and revealed the potential use of AR inhibition as an approach to prevent inflammatory complications. Areas covered: An extensive Internet and Medline search was performed to retrieve information on understanding the role of AR inhibition in the pathophysiology of endotoxin-mediated inflammatory disorders. Overall, inhibition of AR appears to be a promising strategy for the treatment of endotoxemia, sepsis and other related inflammatory diseases. Expert opinion: Current knowledge provides enough evidence to indicate that AR inhibition is a logical therapeutic strategy for the treatment of endotoxin-related inflammatory diseases. Since AR inhibitors have already gone to Phase III clinical studies for diabetic complications and found to be safe for human use, their use in endotoxin-related inflammatory diseases could be expedited. However, one of the major challenges will be the discovery of AR-regulated clinically relevant biomarkers to identify susceptible individuals at risk of developing inflammatory diseases, thereby warranting future research in this area.",
keywords = "Aldose reductase, Endotoxin, Inflammation, Sepsis",
author = "Saumya Pandey and Satish Srivastava and Kota Ramana",
year = "2012",
month = "3",
doi = "10.1517/13543784.2012.656198",
language = "English (US)",
volume = "21",
pages = "329--339",
journal = "Expert Opinion on Investigational Drugs",
issn = "1354-3784",
publisher = "Taylor and Francis Ltd.",
number = "3",

}

TY - JOUR

T1 - A potential therapeutic role for aldose reductase inhibitors in the treatment of endotoxin-related inflammatory diseases

AU - Pandey, Saumya

AU - Srivastava, Satish

AU - Ramana, Kota

PY - 2012/3

Y1 - 2012/3

N2 - Introduction: Aldose reductase (AR) was initially thought to be involved in the secondary diabetic complications because of its glucose-reducing potential. However, evidence from recent studies indicates that AR is an excellent reducer of a number of lipid peroxidation-derived aldehydes as well as their glutathione conjugates, which regulate inflammatory signals initiated by oxidants such as cytokines, growth factors and bacterial endotoxins, and revealed the potential use of AR inhibition as an approach to prevent inflammatory complications. Areas covered: An extensive Internet and Medline search was performed to retrieve information on understanding the role of AR inhibition in the pathophysiology of endotoxin-mediated inflammatory disorders. Overall, inhibition of AR appears to be a promising strategy for the treatment of endotoxemia, sepsis and other related inflammatory diseases. Expert opinion: Current knowledge provides enough evidence to indicate that AR inhibition is a logical therapeutic strategy for the treatment of endotoxin-related inflammatory diseases. Since AR inhibitors have already gone to Phase III clinical studies for diabetic complications and found to be safe for human use, their use in endotoxin-related inflammatory diseases could be expedited. However, one of the major challenges will be the discovery of AR-regulated clinically relevant biomarkers to identify susceptible individuals at risk of developing inflammatory diseases, thereby warranting future research in this area.

AB - Introduction: Aldose reductase (AR) was initially thought to be involved in the secondary diabetic complications because of its glucose-reducing potential. However, evidence from recent studies indicates that AR is an excellent reducer of a number of lipid peroxidation-derived aldehydes as well as their glutathione conjugates, which regulate inflammatory signals initiated by oxidants such as cytokines, growth factors and bacterial endotoxins, and revealed the potential use of AR inhibition as an approach to prevent inflammatory complications. Areas covered: An extensive Internet and Medline search was performed to retrieve information on understanding the role of AR inhibition in the pathophysiology of endotoxin-mediated inflammatory disorders. Overall, inhibition of AR appears to be a promising strategy for the treatment of endotoxemia, sepsis and other related inflammatory diseases. Expert opinion: Current knowledge provides enough evidence to indicate that AR inhibition is a logical therapeutic strategy for the treatment of endotoxin-related inflammatory diseases. Since AR inhibitors have already gone to Phase III clinical studies for diabetic complications and found to be safe for human use, their use in endotoxin-related inflammatory diseases could be expedited. However, one of the major challenges will be the discovery of AR-regulated clinically relevant biomarkers to identify susceptible individuals at risk of developing inflammatory diseases, thereby warranting future research in this area.

KW - Aldose reductase

KW - Endotoxin

KW - Inflammation

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=84856874963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856874963&partnerID=8YFLogxK

U2 - 10.1517/13543784.2012.656198

DO - 10.1517/13543784.2012.656198

M3 - Article

VL - 21

SP - 329

EP - 339

JO - Expert Opinion on Investigational Drugs

JF - Expert Opinion on Investigational Drugs

SN - 1354-3784

IS - 3

ER -