Abstract 8857: Iron Restriction Prevents the Progression of Diabetic Nephropathy in db/db Mice

Abstract

Background: Iron is well-known as an essential trace metal for all living body. On the other hand, excess iron causes oxidative stress through catalyzing highly toxic hydroxyl radical via Fenton/Haber-Weiss reaction. Recent studies have shown that iron reduction ameliorates diabetic condition and prevents development of adipocyte hypertrophy. In the present study, we studied the protective effect of iron reduction against diabetic nephropathy, a diabetic complication. Methods and Results: We employed male db/db mice, a model of diabetic nephropathy and male db/m mice as control mice. db/db mice were divided into 2 groups, normal diet group (ND)(Fe 100mg/kg food) and iron-restricted diet group (ID)(Fe 10mg/kg food). Urinary albumin excretion was increasing in db/db mice with ND compared with db/m mice with ND, which was suppressed in db/db mice with ID. In renal histological analysis, increased glomerular volume and mesangial area expansion in ND-fed db/db mice were reduced in ID-fed db/db mice. Deposition of extracelluar matrix such as collagen IV and fibronectin was decreased in db/db mice with ID. Upregulated glomerular desmin expression in db/db mice with ND was diminished in db/db mice with ID. In terms with oxidative stress, ID diminished increased superoxide production in kidney of ND-fed db/db mice. Renal expression of NADPH oxidase components, p22phox and NOX4, were augmented in db/db mice with ND-fed, which was abolished by ID-fed. In terms with renal iron transporter, there were no differences of expression of transferrin receptor and divalent metal transporter-1 between db/m mice and db/db mice, increased ferroportin expression in db/db mice with ND- was reversed by ID to the same level as db/m mice. Urinary iron excretion was significantly higher in ND-fed db/db mice, which was reduced with ID administration. Conclusion: These findings suggest that dietary iron restriction exert preventive effect against development of diabetic nephropathy via the reduction of oxidative stress.