ly-338522 and Body-Weight

In vitro studies have shown that activation of protein kinase C (PKC) is a key mediator of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) in a range of cell types and in response to high glucose, however, its role in the in vivo setting has not been clearly delineated. Streptozotocin-induced diabetic rats were treated with the PKC-beta isoform inhibitor LY333531 for 8 weeks. LY333531 treatment significantly attenuated increased urinary albumin excretion rate and glomerular volume and tubulointerstitial injury index as well as elevated PKC activity and PKC-beta protein expression in the kidney. Level of malondialdehyde was markedly higher and antioxidant enzyme activity such as superoxide diamutase and catalase as well as glutathione peroxidase were significantly lower in the kidney from diabetic rats than that of the control group. LY333531 administration could remit these changes. Increased macrophages recruitment as well as ICAM-1 and MCP-1 protein expression in the kidney were significantly inhibited by LY333531 in diabetic rats. It is concluded that mechanism of renoprotection of LY333531 may be correlated, at least partly, with suppression of increased macrophages recruitment and overexpression of ICAM-1 and MCP-1 in diabetic rats.

Topics: Albuminuria; Animals; Blood Glucose; Blotting, Western; Body Weight; Chemokine CCL2; Diabetes Mellitus, Experimental; Immunohistochemistry; Indoles; Intercellular Adhesion Molecule-1; Kidney; Kidney Glomerulus; Macrophages; Maleimides; Malondialdehyde; Nephritis, Interstitial; Organ Size; Oxidative Stress; Peroxidases; Protein Kinase C; Protein Kinase C beta; Rats; Rats, Wistar