Reno-Protective Effect of Realgar Nanoparticles on Lupus Nephritis of MRL/Lpr Mice through STAT1

Background: Realgar, an arsenic tetrasulfide compound, is a highly recognized traditional Chinese medicinal prescription that has been widely used to treat various diseases such as inflammatory diseases. However, there are still some problems in the clinical treatment of Realgar, such as large oral...

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Main Authors: Weidong Xu, Zheng Chen, Xiaodong Shen, Chiheng Pi
Format: Article
Language:English
Published: Shiraz University of Medical Sciences 2019-06-01
Series:Iranian Journal of Immunology
Subjects:
Online Access:https://iji.sums.ac.ir/article_44942_abdc837b828419457a1edfbf7f8aab2d.pdf
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author Weidong Xu
Zheng Chen
Xiaodong Shen
Chiheng Pi
author_facet Weidong Xu
Zheng Chen
Xiaodong Shen
Chiheng Pi
author_sort Weidong Xu
collection DOAJ
description Background: Realgar, an arsenic tetrasulfide compound, is a highly recognized traditional Chinese medicinal prescription that has been widely used to treat various diseases such as inflammatory diseases. However, there are still some problems in the clinical treatment of Realgar, such as large oral dose and high potential toxicity. Objective: To evaluate effects of Realgar nanoparticles on lupus nephritis (LN) in vivo in MRL/lpr mice. Methods: Ten-week mice were orally administered every day for eight consecutive weeks except the mice of normal model groups. The serum levels of anti-ds-DNA antibody IgG, IgM, IFN-γ, Creatinine (Cr), and blood urea nitrogen (BUN) were determined, and 24-hour urine protein was also measured. Renal inflammatory pathology analysis was assessed by hematoxylin-eosin (H&E) staining. The expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT 1) and Janus Kinase 1 (JAK 1) in kidney tissue was determined by direct reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Results: The mice treated with Realgar nanoparticle in the high dose-treated (Realgar HD, 0.03 g/kg/d) group exhibited significantly reduced serum levels of anti-dsDNA (p<0.01), IgG (p<0.01), IgM (p<0.01), BUN (p<0.01), Cr (p<0.01), and inflammatory cytokine IFN-γ (p<0.01) as well as proteinuria (p<0.01) compared to the untreated model MRL/lpr mice. Additionally, high doses of Realgar nanoparticles significantly suppressed the phosphorylations of STAT 1 (p<0.01) and the renal pathological changes. Conclusions: The study indicates that Realgar nanoparticles may be a potential agent to treat LN, and the down-regulated p-STAT1 expression suggests that it may be one of the LN treatment targets for Realgar nanoparticles.
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spelling doaj.art-ba45615d5dde46feb3d6d44842e6aaff2022-12-22T03:14:19ZengShiraz University of Medical SciencesIranian Journal of Immunology1735-13831735-367X2019-06-0116217018110.22034/iji.2019.8026044942Reno-Protective Effect of Realgar Nanoparticles on Lupus Nephritis of MRL/Lpr Mice through STAT1Weidong Xu0Zheng Chen1Xiaodong Shen2Chiheng Pi3Department of Rheumatology, The Affiliated Hospital of University of Jiangxi TCM, Jiangxi, ChinaDepartment of Rheumatology, The Affiliated Hospital of University of Jiangxi TCM, Jiangxi, ChinaDepartment of Rheumatology, The Affiliated Hospital of University of Jiangxi TCM, Jiangxi, ChinaFamous Chinese Traditional Medicine Center, The Affiliated Hospital of University of Jiangxi TCM, Jiangxi, ChinaBackground: Realgar, an arsenic tetrasulfide compound, is a highly recognized traditional Chinese medicinal prescription that has been widely used to treat various diseases such as inflammatory diseases. However, there are still some problems in the clinical treatment of Realgar, such as large oral dose and high potential toxicity. Objective: To evaluate effects of Realgar nanoparticles on lupus nephritis (LN) in vivo in MRL/lpr mice. Methods: Ten-week mice were orally administered every day for eight consecutive weeks except the mice of normal model groups. The serum levels of anti-ds-DNA antibody IgG, IgM, IFN-γ, Creatinine (Cr), and blood urea nitrogen (BUN) were determined, and 24-hour urine protein was also measured. Renal inflammatory pathology analysis was assessed by hematoxylin-eosin (H&E) staining. The expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT 1) and Janus Kinase 1 (JAK 1) in kidney tissue was determined by direct reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Results: The mice treated with Realgar nanoparticle in the high dose-treated (Realgar HD, 0.03 g/kg/d) group exhibited significantly reduced serum levels of anti-dsDNA (p<0.01), IgG (p<0.01), IgM (p<0.01), BUN (p<0.01), Cr (p<0.01), and inflammatory cytokine IFN-γ (p<0.01) as well as proteinuria (p<0.01) compared to the untreated model MRL/lpr mice. Additionally, high doses of Realgar nanoparticles significantly suppressed the phosphorylations of STAT 1 (p<0.01) and the renal pathological changes. Conclusions: The study indicates that Realgar nanoparticles may be a potential agent to treat LN, and the down-regulated p-STAT1 expression suggests that it may be one of the LN treatment targets for Realgar nanoparticles.https://iji.sums.ac.ir/article_44942_abdc837b828419457a1edfbf7f8aab2d.pdfjak1/stat1 signaling pathwaylupus nephritismrl/lpr micep-stat 1realgar nanoparticle
spellingShingle Weidong Xu
Zheng Chen
Xiaodong Shen
Chiheng Pi
Reno-Protective Effect of Realgar Nanoparticles on Lupus Nephritis of MRL/Lpr Mice through STAT1
Iranian Journal of Immunology
jak1/stat1 signaling pathway
lupus nephritis
mrl/lpr mice
p-stat 1
realgar nanoparticle
title Reno-Protective Effect of Realgar Nanoparticles on Lupus Nephritis of MRL/Lpr Mice through STAT1
title_full Reno-Protective Effect of Realgar Nanoparticles on Lupus Nephritis of MRL/Lpr Mice through STAT1
title_fullStr Reno-Protective Effect of Realgar Nanoparticles on Lupus Nephritis of MRL/Lpr Mice through STAT1
title_full_unstemmed Reno-Protective Effect of Realgar Nanoparticles on Lupus Nephritis of MRL/Lpr Mice through STAT1
title_short Reno-Protective Effect of Realgar Nanoparticles on Lupus Nephritis of MRL/Lpr Mice through STAT1
title_sort reno protective effect of realgar nanoparticles on lupus nephritis of mrl lpr mice through stat1
topic jak1/stat1 signaling pathway
lupus nephritis
mrl/lpr mice
p-stat 1
realgar nanoparticle
url https://iji.sums.ac.ir/article_44942_abdc837b828419457a1edfbf7f8aab2d.pdf
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AT xiaodongshen renoprotectiveeffectofrealgarnanoparticlesonlupusnephritisofmrllprmicethroughstat1
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