Combination Treatment with Retinoid and Peroxisome Proliferator-Activated Receptors (PPAR)-gamma Agonist on Streptozotocin-Induced Diabetic Nephropathy / 대한신장학회지

ABSTRACT

PURPOSE: An inflammatory mechanism has been suggested to contribute to the progression of diabetic nephropathy. Both retinoid and PPAR-gamma agonist, known anti-inflammatory agents, have been reported to be beneficial in diabetic nephropathy. Because they form heterodimer for transcription within the nucleus, we investigated the effect of a combination treatment with them in streptozotocin (STZ)-induced diabetic rats. METHODS: STZ-induced diabetic rats were treated with retinoid and PPAR-gamma agonist. The effects were determined by measuring urinary monocyte chemoattractant peptide (MCP)-1, proteinuria, and intrarenal ED-1 expression. RESULTS: Blood glucose concentration was higher in diabetic rats than in control rats. Retinoid and PPAR-gamma agonist did not affect blood glucose concentration. Urinary protein excretion (8.6+/-0.69 vs. 22.1 mg/mgCr, p<0.01) and urinary MCP-1 (19.8+/-3.4 vs. 61.5+/-6.1 pg/mgCr, p<0.01) were significantly higher in diabetic rats at four weeks after the induction of diabetes compared with controls. Proteinuria in the group with retinoic acid (16.9+/-1.4, mg/mgCr, p<0.05) and PPAR-gamma agonist (14.6+/-1.5 mg/mgCr, p<0.05) were decreased. Retinoic acid (42.2+/-2.7 pg/mgCr, p<0.05) and PPAR-gamma agonist (40.5+/-pg/ mgCr, p<0.05) significantly suppressed MCP-1 level in diabetic rats. However, combination treatment was not effective to proteinuria and urinary MCP-1 concentration. Urinary protein excretion was significantly correlated with MCP-1 (r=0.9, p<0.01). Immunohistochemistry revealed a significant increase in staining for ED-1 protein in the diabetic kidneys. Both retinoid and PPAR-gamma agonist significantly suppressed intrarenal ED-1 synthesis. However combination treatment didn't show any additional beneficial effects. CONCLUSION: Both retinoic acid and PPAR-gamma agonist suppressed proteinuria and inflammatory changes in diabetic rats. However, there were no additional effects of the combination treatment present. Further research is needed to determine the effect of the combination treatment on diabetic nephropathy.