title: Iron restriction prevents diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rat.
abstract: High body iron levels are found in type 2 diabetes mellitus (DM). Iron excess leads to tissue injury through free radical formation. We investigated the effect of iron restriction on renal damage in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 DM. OLETF rats (n = 18) were divided into three groups at 10 weeks of age: high fat diet containing 8% NaCl (HFS, n = 6), HFS diet with iron restricted (HFS + IR, n = 6), and HFS with hydralazine (HFS + Hyd, n = 6). Long-Evans Tokushima (LETO) rats served as control. Iron restriction decreased hemoglobin levels, systolic blood pressure, and urinary excretion of protein and 8-hydroxy-2'-deoxyguanosine in the OLETF rats fed with HFS diet. Compared to the HFS group, the expression of desmin, renal glomerular injury marker and iron deposition in the renal tubules were attenuated in the HFS + IR group but not in the HFS + Hyd group at 26 weeks of age. Moreover, renal hypoxia (evaluated as pimonidazole adducts) was improved in the HFS + IR group compared to the HFS group in spite of anemia. Iron restriction prevented the production of reactive oxygen species and the development of early stage nephropathy in OLETF rats. Iron restriction may be beneficial in prevention of nephropathy in type 2 DM.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Sasaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Akahori
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Naito
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006830:Hydralazine / Q000008:administration & dosage; D019266:Iron, Dietary / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D020334:Rats, Inbred OLETF
chemical_list: D000959:Antihypertensive Agents; D019266:Iron, Dietary; D006830:Hydralazine