Abstract | OBJECTIVES: In this study, we aimed to ascertain the efficacy and determine the dose effects of a new analog of vitamin D, 2α-methyl-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2AMD), in decreasing fibrosis and improving renal function in a rat model of kidney disease. MATERIALS AND METHODS: Using the cyclosporine model of chronic kidney disease, we tested 4 dose regimens (2.5, 5, 10, and 20 ng/kg) of 2AMD by subcutaneous administration. The 2AMD analog was compared with another analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD), given at 5 ng/kg. RESULTS: After 28 days of cyclosporine administration with 5 ng/kg 2AMD or 2MD, blood urea nitrogen levels were decreased by 20% and 30%, with no increase in serum calcium. This dose significantly decreased collagen levels by 50%, as determined by relative measurements of birefringence elicited under polarized light following picrosirius red staining of kidney tissues. The 20 ng/kg dose of 2AMD was hypercalcemic, with consequent deleterious effects on measured parameters; however, all doses of 2AMD tested decreased collagen as determined by picrosirius staining. In Western blot analysis of extracts from rat kidneys treated with cyclosporine and 5 ng/kg 2AMD, the fibrotic markers, fibronectin and vimentin, were decreased compared with animals treated only with cyclosporine. CONCLUSIONS: We found that both vitamin D analogs are potent inhibitors of kidney fibrosis with potential renoprotective activity.
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Authors | Bianca Tomasini-Johansson, Cori O'Brien, Alexandra Larson-Osborne, Inger Toraason, Debra Hullett, Lori Plum, Hector DeLuca, Hans Sollinger |
Journal | Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation
(Exp Clin Transplant)
Vol. 15
Issue 6
Pg. 641-647
(Dec 2017)
ISSN: 2146-8427 [Electronic] Turkey |
PMID | 29219791
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- 2-methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D3
- Fibronectins
- Immunosuppressive Agents
- Renal Agents
- Vimentin
- Cyclosporine
- Collagen
- Calcitriol
- Calcium
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Topics |
- Animals
- Blood Urea Nitrogen
- Calcitriol
(analogs & derivatives, pharmacology)
- Calcium
(blood)
- Collagen
(metabolism)
- Cyclosporine
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Fibronectins
(metabolism)
- Fibrosis
- Immunosuppressive Agents
- Kidney
(drug effects, metabolism, pathology, physiopathology)
- Male
- Rats, Sprague-Dawley
- Renal Agents
(pharmacology)
- Renal Insufficiency, Chronic
(blood, chemically induced, drug therapy, pathology)
- Vimentin
(metabolism)
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