Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome

Abstract Background Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians. Methods Adriamycin (ADR) wa...

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Main Authors: Juan Lv, Guozhong Xue, Yunxia Zhang, Xinbin Wang, Enlai Dai
Format: Article
Language:English
Published: BMC 2023-01-01
Series:European Journal of Medical Research
Subjects:
Online Access:https://doi.org/10.1186/s40001-022-00973-9
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author Juan Lv
Guozhong Xue
Yunxia Zhang
Xinbin Wang
Enlai Dai
author_facet Juan Lv
Guozhong Xue
Yunxia Zhang
Xinbin Wang
Enlai Dai
author_sort Juan Lv
collection DOAJ
description Abstract Background Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians. Methods Adriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro. Results The contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway. Conclusion ICA enhances the therapeutic effect of DEX on the nephrotic syndrome.
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spelling doaj.art-4f7014836e7a45adb67bb529334c3e482023-01-29T12:07:31ZengBMCEuropean Journal of Medical Research2047-783X2023-01-012811710.1186/s40001-022-00973-9Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndromeJuan Lv0Guozhong Xue1Yunxia Zhang2Xinbin Wang3Enlai Dai4Department of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese MedicineDepartment of Nephrology, Affiliated Hospital of Gansu University of Chinese MedicineDepartment of Neurology, Gansu Provincial Hospital of TCMDepartment of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese MedicineDepartment of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese MedicineAbstract Background Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians. Methods Adriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro. Results The contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway. Conclusion ICA enhances the therapeutic effect of DEX on the nephrotic syndrome.https://doi.org/10.1186/s40001-022-00973-9AdriamycinAutophagyPodocyte injuryNephrotic syndrome
spellingShingle Juan Lv
Guozhong Xue
Yunxia Zhang
Xinbin Wang
Enlai Dai
Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome
European Journal of Medical Research
Adriamycin
Autophagy
Podocyte injury
Nephrotic syndrome
title Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome
title_full Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome
title_fullStr Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome
title_full_unstemmed Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome
title_short Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome
title_sort icariin synergizes therapeutic effect of dexamethasone on adriamycin induced nephrotic syndrome
topic Adriamycin
Autophagy
Podocyte injury
Nephrotic syndrome
url https://doi.org/10.1186/s40001-022-00973-9
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AT yunxiazhang icariinsynergizestherapeuticeffectofdexamethasoneonadriamycininducednephroticsyndrome
AT xinbinwang icariinsynergizestherapeuticeffectofdexamethasoneonadriamycininducednephroticsyndrome
AT enlaidai icariinsynergizestherapeuticeffectofdexamethasoneonadriamycininducednephroticsyndrome