Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin Nephrosis

Background/Aims: Although high salt intake is thought to accelerate renal progression in proteinuric kidney disease, it is not known whether strict dietary salt restriction could delay renal inflammation and interstitial fibrosis. Here, we sought to answer this question in a rat model of adriamycin-...

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Main Authors: Joon-Sung Park, Sua Kim, Chor Ho Jo, Il Hwan Oh, Gheun-Ho Kim
Format: Article
Language:English
Published: Karger Publishers 2014-07-01
Series:Kidney & Blood Pressure Research
Subjects:
Online Access:http://www.karger.com/Article/FullText/355782
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author Joon-Sung Park
Sua Kim
Chor Ho Jo
Il Hwan Oh
Gheun-Ho Kim
author_facet Joon-Sung Park
Sua Kim
Chor Ho Jo
Il Hwan Oh
Gheun-Ho Kim
author_sort Joon-Sung Park
collection DOAJ
description Background/Aims: Although high salt intake is thought to accelerate renal progression in proteinuric kidney disease, it is not known whether strict dietary salt restriction could delay renal inflammation and interstitial fibrosis. Here, we sought to answer this question in a rat model of adriamycin-induced nephrotic syndrome. Methods: Adriamycin was administered via the femoral vein in a single bolus (7.5 mg/kg), and the rats were put on a sodium-deficient rodent diet. Rats with intact kidneys were studied for 5 weeks (experiment 1), and uninephrectomized rats were studied for 6 weeks (experiment 2). Results: In experiment 1, restricting salt intake improved renal tubulointerstitial histopathology in adriamycin-treated rats. Immunohistochemical and immunoblot results additionally showed that restricting dietary salt lowered adriamycin-induced expression of osteopontin, collagen III, and fibronectin. In experiment 2, salt restriction improved adriamycin-induced azotemia, although it did not affect proteinuria or blood pressure. Dietary salt restriction also reduced adriamycin-induced infiltration of ED1-positive cells and the upregulated expression of osteopontin and a-SMA. Masson's trichrome and Sirius red staining revealed that salt restriction slowed Adriamycin-induced progression of renal interstitial fibrosis. Finally, qPCR revealed that adriamycin-induced expression of TNF-a, IκB-a, gp91phox, p47phox, and p67phox mRNA was blocked by salt restriction. Conclusion: Our findings demonstrate that strict dietary salt restriction delays the progress of renal inflammation and fibrosis in proteinuric kidney disease, most likely via relieving the reactive oxygen species-mediated NF-κB activation.
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spelling doaj.art-69b9a60dec6740b0ae6aaaaa1763ba572022-12-22T00:01:27ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432014-07-01391869610.1159/000355782355782Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin NephrosisJoon-Sung ParkSua KimChor Ho JoIl Hwan OhGheun-Ho KimBackground/Aims: Although high salt intake is thought to accelerate renal progression in proteinuric kidney disease, it is not known whether strict dietary salt restriction could delay renal inflammation and interstitial fibrosis. Here, we sought to answer this question in a rat model of adriamycin-induced nephrotic syndrome. Methods: Adriamycin was administered via the femoral vein in a single bolus (7.5 mg/kg), and the rats were put on a sodium-deficient rodent diet. Rats with intact kidneys were studied for 5 weeks (experiment 1), and uninephrectomized rats were studied for 6 weeks (experiment 2). Results: In experiment 1, restricting salt intake improved renal tubulointerstitial histopathology in adriamycin-treated rats. Immunohistochemical and immunoblot results additionally showed that restricting dietary salt lowered adriamycin-induced expression of osteopontin, collagen III, and fibronectin. In experiment 2, salt restriction improved adriamycin-induced azotemia, although it did not affect proteinuria or blood pressure. Dietary salt restriction also reduced adriamycin-induced infiltration of ED1-positive cells and the upregulated expression of osteopontin and a-SMA. Masson's trichrome and Sirius red staining revealed that salt restriction slowed Adriamycin-induced progression of renal interstitial fibrosis. Finally, qPCR revealed that adriamycin-induced expression of TNF-a, IκB-a, gp91phox, p47phox, and p67phox mRNA was blocked by salt restriction. Conclusion: Our findings demonstrate that strict dietary salt restriction delays the progress of renal inflammation and fibrosis in proteinuric kidney disease, most likely via relieving the reactive oxygen species-mediated NF-κB activation.http://www.karger.com/Article/FullText/355782FibrosisDietary NaClDoxorubucinNF-kappa BNADPH oxidase
spellingShingle Joon-Sung Park
Sua Kim
Chor Ho Jo
Il Hwan Oh
Gheun-Ho Kim
Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin Nephrosis
Kidney & Blood Pressure Research
Fibrosis
Dietary NaCl
Doxorubucin
NF-kappa B
NADPH oxidase
title Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin Nephrosis
title_full Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin Nephrosis
title_fullStr Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin Nephrosis
title_full_unstemmed Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin Nephrosis
title_short Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin Nephrosis
title_sort effects of dietary salt restriction on renal progression and interstitial fibrosis in adriamycin nephrosis
topic Fibrosis
Dietary NaCl
Doxorubucin
NF-kappa B
NADPH oxidase
url http://www.karger.com/Article/FullText/355782
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