The Anti-inflammatory Effect of Retinoid on Streptozotocin-induced Diabetic Nephropathy

Han, Sang Youb; Ji, Yi Hwa; So, Kyeong A; Han, Kum Hyun; Kang, Young Sun; Cha, Dae Ryong; Kim, Hyoung Kyu; Han, Jee Young

Abstract

BACKGROUND
An inflammatory mechanism has been suggested to contribute to the progression of diabetic nephropathy. Although retinoid, a known anti-inflammatory agent, has been reported to be beneficial in some experimental renal diseases, it has not been shown whether it prevents disease progression in diabetic nephropathy. Therefore, we investigated whether all-trans retinoic acid inhibits inflammatory changes and improves renal function during the early stages of diabetic nephropathy in streptozotocin-induced diabetic rats. METHODS: We evaluated anti-inflammatory effect of retinoid on streptozotocin-induced diabetic nephropathy. Anti-inflammatory effect was determined by the expression of monocyte chemoattractant peptide-1 (MCP-1). RESULTS: Urinary protein excretion was significantly higher in diabetic rats at four weeks after the induction of diabetes mellitus compared with controls, and proteinuria in the group with retinoic acid treatment was decreased (1.25+/-0.69 vs. 0.78+/-0.72 mg/mg Cr, p=0.056). Urinary excretion of MCP-1 was rapidly increased at two days after induction of diabetes mellitus in diabetic rats, and further increased until four weeks of age compared with control rats. Retinoic acid treatment suppressed to 30% reduction of the urinary level of MCP-1 compared with vehicle treated diabetic rats (119.3+/-74.2 vs. 78.1+/-62.7 pg/mg Cr, p=0.078). Immunohistochemistry revealed a significant increase in staining for MCP-1 protein in the diabetic kidney, and retinoic acid treatment significantly suppressed intrarenal MCP-1 protein synthesis. CONCLUSION: Retinoic acid suppressed proteinuria and inflammatory changes in diabetic rats. These results suggest that retinoic acid may have an anti- inflammatory effect in diabetic nephropathy.