Kosin Medical Journal

Original articles

Effects of cholecalciferol and omega-3 fatty acids on hepcidin levels in 5/6 nephrectomy rats: Yu In Jeong, Hyo Jin Jung, Mi Hwa Lee, Young Ki Son, Seong Eun Kim, Won Suk An, Su Mi Lee; Kosin Med J. 2024;39(1):35-43. Published online September 25, 2023; DOI: https://doi.org/10.7180/kmj.23.137

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Abstract PDF PubReader ePub: 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.

Omega-3 fatty acids upregulate Nrf2 expression and attenuate apoptosis, inflammation, and fibrosis in a rat model of cyclosporine-induced nephropathy: Ji Young Lee, Young Ki Son, Mi Hwa Lee, Su Mi Lee, Seong Eun Kim, Won Suk An; Kosin Med J. 2023;38(3):184-192. Published online July 26, 2023; DOI: https://doi.org/10.7180/kmj.23.112

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Background
Cyclosporine A (CsA)-induced kidney injury is characterized by renal impairment with inflammatory cell infiltrations, apoptosis, fibrosis, and hypoxic injury. It is not clear whether omega-3 fatty acids (O-3 FAs), which have anti-inflammatory and antioxidant roles, affect nuclear factor erythroid 2-related factor 2 (Nrf2) expression. The aim of this study was to investigate whether O-3 FAs affect Nrf2 expression and exert anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in CsA-induced nephropathy.
Methods
Male Sprague-Dawley rats were divided into control, CsA-treated, and CsA-treated with O-3 FA groups. Nrf2 expression was measured by Western blots and immunohistochemical staining.
Results
Kidney function was impaired in the CsA-treated rats compared to the controls. Caspase-3 and caspase-7 were activated in the CsA-treated group, and the Bax/Bcl2 ratio was higher. O-3 FAs attenuated these apoptosis-related changes. ED-1 and inhibition of kappa B (IĸB) protein expression were significantly upregulated in the CsA-treated group. Compared to the control group, O-3 FA supplementation attenuated the increased expression of ED-1 and IĸB related to inflammation. Smad2/3, Smad4, and transforming growth factor-β1 were activated in the CsA group, and O-3 FA treatment prevented these changes related to renal fibrosis. The expression of Nrf2 was reduced in CsA-treated rats, but Nrf-2 was increased by O-3 FA treatment.
Conclusions
We suggest that Nrf2 is a potential mediator induced by O-3 FA supplementation and that it attenuates pro-inflammatory pathways, fibrotic processes, and apoptosis. Further studies are needed to elucidate the crosstalk between Nrf2 expression and signals related to O-3 FA treatment.

Citations

Citations to this article as recorded by

Omega-3 fatty acids: promising therapeutic agents for combating kidney injuries
Hee-Jae Cha
Kosin Medical Journal.2023; 38(3): 157. CrossRef

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