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

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.