Background:
Iron, an essential trace metal for organisms, catalyzes highly toxic hydroxyl radical via Fenton/Haber-Weiss reaction. We recently have clarified that iron chelation prevents the development of adipocyte hypertrophy through the reduction of oxidative stress in diabetic obese mice. It is suggested that iron reduction potentiates to be beneficial effects against diabetic complications. In the present study, we investigated the protective action of iron restriction against the progression of diabetic nephropathy.
METHODS:
We employed and divided male db/db mice of 8 weeks old age, a model of diabetic nephropathy, into 2 groups, normal diet group (Fe 100mg/kg food; ND) and low iron diet group (Fe 10mg/kg food; LID). After 8 weeks treatment, the mice were used for analysis.
Results:
LID group showed the decreased renal iron content (7.5±3.0 μg/g tissue vs 5.7±0.3 μg/g tissue, ND vs LID, p<0.05), serum iron concentration (213±15 μg/dL vs 157±14 μg/dL, ND vs LID, p<0.05) and hemoglobin level (13.5±0.7g/dL vs 10.4±0.5g/dL, ND vs LID, p<0.01). Urinary albumin excretion was significantly decreased in LID group compared to ND group (2.6±0.4mg/g·Cre vs 1.4±0.3mg/g·Cre, ND vs LID, p<0.05). In histological analysis, mesangial proliferation was ameliorated in db/db mice with LID (39% vs 28%, ND vs LID, p<0.05). LID reduced the deposition of collagen IV, fibronectin and desmin by 61%, 60%, and 42%, respectively, in glomeruli of db/db mice. Superoxide production, p22phox and NOX4 expression were also diminished in kidney of LID group.
Conclusion:
Iron restriction is suggested to prevent the development of diabetic nephropathy through the suppression of oxidative stress.
Clinical Characteristics, Residual Beta-Cell Function and Pancreatic Auto-Antibodies in Thai people with Long-Standing Type 1 Diabetes Mellitus
