Volume 25, Issue 6 (11-2021)                   IBJ 2021, 25(6): 417-425 | Back to browse issues page

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Romi M M, Arfian N, Setyaningsih W A W, Putri R G P, Juffrie M, Sari D C R. Calcitriol Treatment Attenuates Uric Acid-Induced Kidney Injury via Super Oxide Dismutase-1 (SOD-1) Upregulation and Fibrosis Reduction. IBJ 2021; 25 (6) :417-425
URL: http://ibj.pasteur.ac.ir/article-1-3184-en.html
Calcitriol Treatment Attenuates Uric Acid-Induced Kidney Injury via Super Oxide Dismutase-1 (SOD-1) Upregulation and Fibrosis Reduction
Muhammad Mansyur Romi , Nur Arfian , Wiwit Ananda Wahyu Setyaningsih , Rachma Greta Perdana Putri , Mohammad Juffrie , Dwi Cahyani Ratna Sari
Abstract:  
Background: Hyperuricemia induces nephropathy through the mediation of oxidative stress, tubular injury, inflammation, and fibrosis. The high uric acid level is associated with the reduction of vitamin D levels. However, the reno-protective effects of this vitamin in hyperuricemia condition remain unknown. This study aimed to elucidate calcitriol treatment in a uric acid-induced hyperuricemia mice model. Methods: Uric acid (125 mg/kg body weight [BW]) was administered intraperitoneally for 7 (UA7) and 14 (UA14) days. Calcitriol (0.5 mg/kg BW) was intraperitoneally injected for the following seven days, after 14 days of uric acid induction (UA14VD7 group). The control group received NaCl 0.9%, by the same route. Serum creatinine was measured using calorimetric method, and uric acid levels were assessed using enzymatic calorimetric assay. Tubular injury and fibrosis were assessed using PAS and Sirius red staining. RT-PCR and real-time reverse transcription PCR were carried out for the analyses of SOD-1, Collagen-1, and TGF-b1 mRNA expression in the kidney. Immunostaining of super oxide dismutase type 1 (SOD-1) was performed to detect its expression in the kidney. Results: Uric acid and creatinine levels markedly increased in UA14 groups, followed by an exacerbation of tubular injury. RT-PCR revealed the upregulation of Collagen-1 and TGF-b1, along with the downregulation of SOD-1. Calcitriol treatment attenuated the injury with reducing uric acid and creatinine levels, as well as tubular injury. This was associated with lower Collagen-1 and TGF-b1 mRNA expression compared to the UA7 and UA14 groups. SOD-1 was upregulated in epithelial cells in the UA14VD7 group. Conclusion: Calcitriol treatment after uric acid induction may attenuate kidney injury through upregulation of SOD-1 and downregulation of Collagen-1 and TGF-b1 gene expression.
Keywords: Fibrosis, Hyperuricemia, Kidney injury, Superoxide dismutase-1, Vitamin D
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Type of Study: Full Length/Original Article | Subject: Medical Biotechnology
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