Effects of curcumin on diabetes-induced leukocyte-endothelium interaction: roles of nox2 enzyme and thioredoxin-interacting protein

Abstract

Hyperglycemia increases thioredoxin-interacting protein (Txnip) expression that causes cellular redox imbalance. In addition, the up-regulation of Txnip can enhance vascular cell adhesion molecules expression such as intercellular adhesion molecule-1 (ICAM-1) which leads to increase leukocyte-endothelium interaction to promote vascular inflammation. Moreover, the leukocyte accumulation in microcirculation causes endothelial damage by NADPH oxidase enzyme (NOX2). Curcumin is a polyphenolic compound which exhibits antioxidant, and anti-inflammatory properties. The present study aimed to study the mechanisms of curcumin on preventing diabetes-induced leukocyte-endothelium interaction in association with its actions on NOX2 enzyme and Txnip expressions. Male Wistar rats were divided into four groups: control-treated with corn oil group (CON), control-treated with curcumin group (CONCUR, 300mg/kgBW), diabetic-treated with corn oil group (DM; streptozotocin (STZ), i.v. 55 mg/kg BW), and diabetes-treated with curcumin (DMCUR). The supplementation of curcumin was started at 10 days after STZ-injection. Then on the 12th week after STZ injection, iris blood perfusion and leukocyte adhesion at iris of each rat was measured by using laser Doppler and intravital fluorescent microscopy, respectively. Plasma glucose and HbA1c were also determined by using enzymatic and turbidimetric immunoinhibition methods, respectively. P47phox expression (marker of NOX2 enzyme activation), Txnip expression, and malondialdehyde (MDA) level at eye fundus were determined by Western Blot analysis and TBAR assay, respectively. The results showed that body weight and iris blood perfusion of DM and DMCUR were decreased significantly as compared to CON (P < 0.001), but plasma glucose and HbA1c of DM and DMCUR were increased significantly as compared to CON (P < 0.001). Interestingly, the leukocyte adhesion, p47phox expression, and MDA level in DM were increased significantly as compared to CON (P < 0.05), but decreased significantly when compared to DMCUR (P < 0.05). It is concluded that 300 mg/kgBW curcumin could ameliorate diabetic vascular inflammation by decreasing ROS overproduction, reducing leukocyte-endothelium interaction, and also inhibiting NOX2 activation. However, it could not significantly reduce blood glucose, Txnip expression, and increase iris blood perfusion.