The effect of dietary iron restriction against diabetic nephropathy in db/db mice

Abstract

Recently body iron reduction has been shown to ameliorate obese and diabetes. In the present study, we tested the protective effects of dietary iron restriction against diabetic nephropathy Male db/db mice at 8 week‐old age, a model of diabetic nephropathy, were divided into 2 groups and fed a normal diet (ND) or a low iron diet (LID) and male db/m mice with ND were employed as control mice. Increasing urinary albumin excretion was observed in db/db mice with ND, but this was suppressed in db/db mice with LID. Histologically, the db/db mice in the ND group had increased glomerular size and mesangial expansion compared to the LID group. Augmented deposition of extracellular matrixes was decreased in db/db mice with LID. Increased superoxide production observed in the kidneys of the ND db/db mice was diminished in the LID group. NADPH oxidase activity and expression of NADPH oxidase components p22phox and NOX4 were augmented in kidney of the ND group, and these were abolished by LID. Renal expression of ferroportin and ferritin heavy chain increased in the kidneys of the db/db mice. Serum iron concentration and urinary iron excretion was significantly higher in ND db/db mice compared to db/m mice and was diminished in the LID group. Taken together, dietary iron restriction exerts a preventive action against the development of diabetic nephropathy through oxidative stress reduction.