title: Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice.
abstract: Excess iron causes oxidative stress through hydroxyl-radical production via Fenton/Haber-Weiss reactions. Recently, body iron reduction has been found to ameliorate diabetes. In the present study, we examined the protective effect of dietary iron restriction against diabetic nephropathy in the db/db mouse model of diabetic nephropathy using db/m mice as controls. The db/db mice were divided into two groups and fed a normal diet (ND) or a low-iron diet (LID). Increasing urinary albumin excretion was observed in the ND db/db mice, but this was suppressed in db/db mice with LID. Histologically, the db/db mice in the ND group had increased glomerular volume and mesangial area compared with the LID group. Augmented deposition of extracellular matrixes was decreased in db/db mice with LID. In terms of oxidative stress, increased superoxide production observed in the kidneys of the ND db/db mice was diminished in the LID group. NADPH oxidase activity and renal expression of NADPH oxidase components p22(phox) and NADPH oxidase 4 (NOX4) were augmented in the ND group, and this was abolished by LID. There were no differences in expression of renal iron importers, transferrin receptor, or divalent metal transporter-1 between db/m mice and db/db mice. The level of ferroportin, an iron exporter, increased in the kidneys of the db/db mice. Urinary iron excretion was significantly higher in ND db/db mice and was reduced in the LID group. These findings suggest that dietary iron restriction exerts a preventive effect on the progression of diabetic nephropathy partly due to the reduction of oxidative stress.
authors: Department of Pharmacology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan. yasuike@tokushima-u.ac.jp
authors: Yasumasa
authors: Y
authors: Ikeda
authors: Hideaki
authors: H
authors: Enomoto
authors: Soichiro
authors: S
authors: Tajima
authors: Yuki
authors: Y
authors: Izawa-Ishizawa
authors: Yoshitaka
authors: Y
authors: Kihira
authors: Keisuke
authors: K
authors: Ishizawa
authors: Shuhei
authors: S
authors: Tomita
authors: Koichiro
authors: K
authors: Tsuchiya
authors: Toshiaki
authors: T
authors: Tamaki
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D003573:Cytochrome b Group / Q000096:biosynthesis; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control*; D019266:Iron, Dietary / Q000008:administration & dosage* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D003573:Cytochrome b Group; D019266:Iron, Dietary; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; C515614:Cyba protein, mouse