Kosin Med J.  2024 Mar;39(1):35-43. 10.7180/kmj.23.137.

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

• Jeong YI
• Jung HJ
• Lee MH
• Son YK
• Kim SE
• An WS
• Lee SM

• KMID: 2556796
• DOI: http://doi.org/10.7180/kmj.23.137

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.

Keyword

Anemia; Cholecalciferol; Chronic kidney disease; Hepcidins; Omega-3 fatty acid

Figure

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  Fig. 1. (A) Hepcidin expression in the kidney of 5/6 nephrectomy (Nx) rats. (B) Immunohistochemical staining (×200) of hepcidin in the kidney of sham control rats, (C) 5/6 Nx rats, (D) 5/6 Nx rats treated with cholecalciferol, (E) 5/6 Nx rats treated with omega-3 fatty acids, and (F) 5/6 Nx rats treated with cholecalciferol and omega-3 fatty acids. O, omega-3 fatty acid; V, vitamin D. a)p<0.05, compared to the control group; b)p<0.05, compared to the 5/6 Nx group.

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  Fig. 2. Ferroportin and interlukin-6 (IL-6) expression in the kidney of 5/6 nephrectomy (Nx) rats. O, omega-3 fatty acid; V, vitamin D. a)p<0.05, compared to the control group; b)p<0.05, compared to the 5/6 Nx group.

• 

  Fig. 3. Hepcidin, ferroportin and interlukin-6 (IL-6) expression in the liver of 5/6 nephrectomy (Nx) rats. O, omega-3 fatty acid; V, vitamin D. a)p<0.05, compared to the control group; b)p<0.05, compared to the 5/6 Nx group.

Reference

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