The aldose reductase inhibitor fidarestat suppresses ischemia-reperfusion-induced inflammatory response in rat retina.
Recent studies suggest that increased aldose reductase (AR) activity plays an important role in ischemia-reperfusion injury in the retina. The mechanisms are not completely understood, but may be linked to inflammation. In the present study, we investigated whether the AR inhibitor fidarestat suppressed the retinal inflammatory response induced by ischemia-reperfusion in a rat model. The inflammatory response was manifested by increased gene expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 (ICAM-1) as well as elevated protein levels of soluble ICAM-1. This response was partially suppressed by the AR inhibitor fidarestat. The findings may reveal beneficial effects of AR inhibition on retinal inflammation associated with ischemia-reperfusion and are in agreement with recent developments in pharmacological research suggesting that pathological conditions other than diabetes may benefit from AR inhibitors.
Agardh
Carl-David
CD
Department of Clinical Sciences, University Hospital MAS, Lund University, SE-205 02 Malmo, Sweden. carl-david.agardh@med.lu.se
Agardh
Elisabet
E
Obrosova
Irina G
IG
Smith
Maj-Lis
ML
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D005260:Female; D015870:Gene Expression; D048289:Imidazolidines / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D048289:Imidazolidines; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C077139:fidarestat; D000449:Aldehyde Reductase