Effects of cholecalciferol and omega-3 fatty acids on hepcidin levels in 5/6 nephrectomy rats

Abstract

Background: Anemia is a common complication of chronic kidney disease (CKD). In patients with CKD-related anemia, an inverse relationship between vitamin D and hepcidin levels has been observed. Hepcidin is a key regulator of iron homeostasis, mediated via binding to ferroportin. The aim of this study was to investigate the effects of cholecalciferol and omega-3 fatty acids (FA) on hepcidin levels using 5/6 nephrectomized (Nx) rats.Methods: Male Sprague-Dawley rats were divided into five groups: sham control, 5/6 Nx, 5/6 Nx treated with cholecalciferol, 5/6 Nx treated with omega-3 FA, and 5/6 Nx treated with both cholecalciferol and omega-3 FA. We measured the hepcidin and ferroportin levels in the kidney and liver by enzyme-linked immunosorbent assays and Western blots. We evaluated hepcidin expression in the kidney by immunohistochemical staining.Results: Among the five groups, 5/6 Nx rats exhibited the worst kidney function. Compared with the sham controls, 5/6 Nx rats showed significantly increased serum hepcidin levels and decreased vitamin D levels. Supplementation with either omega-3 FA or cholecalciferol decreased hepcidin and increased vitamin D levels, with a concurrent improvement of anemia. Furthermore, 5/6 Nx rats treated with omega-3 FA/cholecalciferol showed decreased ferroportin and ferritin levels, while iron and total iron-binding capacity levels increased.Conclusions: Treatment with a combination of cholecalciferol and omega-3 FA may improve anemia in a CKD rat model by decreasing hepcidin levels.