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Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI

Aims: To evaluate the utility of fasudil in a rat model of contrast-associated acute kidney injury (CA-AKI) and explore its underlying mechanism through multiparametric renal magnetic resonance imaging (mpMRI). Methods: Experimental rats (n = 72) were grouped as follows: controls (n = 24), CA-AKI (n...

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Autores principales: Wang, Bin, Wang, Yongfang, Tan, Yan, Guo, Jinxia, Chen, Haoyuan, Wu, Pu-Yeh, Wang, Xiaochun, Zhang, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242620/
https://www.ncbi.nlm.nih.gov/pubmed/35784704
http://dx.doi.org/10.3389/fphar.2022.905547
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author Wang, Bin
Wang, Yongfang
Tan, Yan
Guo, Jinxia
Chen, Haoyuan
Wu, Pu-Yeh
Wang, Xiaochun
Zhang, Hui
author_facet Wang, Bin
Wang, Yongfang
Tan, Yan
Guo, Jinxia
Chen, Haoyuan
Wu, Pu-Yeh
Wang, Xiaochun
Zhang, Hui
author_sort Wang, Bin
collection PubMed
description Aims: To evaluate the utility of fasudil in a rat model of contrast-associated acute kidney injury (CA-AKI) and explore its underlying mechanism through multiparametric renal magnetic resonance imaging (mpMRI). Methods: Experimental rats (n = 72) were grouped as follows: controls (n = 24), CA-AKI (n = 24), or CA-AKI + Fasudil (n = 24). All animals underwent two mpMRI studies (arterial spin labeling, T1 and T2 mapping) at baseline and post iopromide/fasudil injection (Days 1, 3, 7, and 13 respectively). Relative change in renal blood flow (ΔRBF), T1 (ΔT1) and T2 (ΔT2) values were assessed at specified time points. Serum levels of cystatin C (CysC) and interleukin-1β (IL-1β), and urinary neutrophil gelatinase-associated lipocalin (NGAL) concentrations were tested as laboratory biomarkers, in addition to examining renal histology and expression levels of various proteins (Rho-kinase [ROCK], α-smooth muscle actin [α-SMA]), hypoxia-inducible factor-1α (HIF-1α), and transforming growth factor-β1 (TGF-β1) that regulate renal fibrosis and hypoxia. Results: Compared with the control group, serum levels of CysC and IL-1β, and urinary NGAL concentrations were clearly increased from Day 1 to Day 13 in the CA-AKI group (all p < 0.05). There were significant reductions in ΔT2 values on Days 1 and 3, and ΔT1 reductions were significantly more pronounced at all time points (Days 1–13) in the CA-AKI + Fasudil group (vs. CA-AKI) (all p < 0.05). Fasudil treatment lowered expression levels of ROCK-1, and p-MYPT1/MYPT1 proteins induced by iopromide, decreasing TGF-β1 expression and suppressing both extracellular matrix accumulation and α-SMA expression relative to untreated status (all p < 0.05). Fasudil also enhanced PHD2 transcription and inhibition of HIF-1α expression after CA-AKI. Conclusions: In the context of CA-AKI, fasudil appears to reduce renal hypoxia, fibrosis, and dysfunction by activating (Rho/ROCK) or inhibiting (TGF-β1, HIF-1α) certain signaling pathways and reducing α-SMA expression. Multiparametric MRI may be a viable noninvasive tool for monitoring CA-AKI pathophysiology during fasudil therapy.
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spelling pubmed-92426202022-06-30 Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI Wang, Bin Wang, Yongfang Tan, Yan Guo, Jinxia Chen, Haoyuan Wu, Pu-Yeh Wang, Xiaochun Zhang, Hui Front Pharmacol Pharmacology Aims: To evaluate the utility of fasudil in a rat model of contrast-associated acute kidney injury (CA-AKI) and explore its underlying mechanism through multiparametric renal magnetic resonance imaging (mpMRI). Methods: Experimental rats (n = 72) were grouped as follows: controls (n = 24), CA-AKI (n = 24), or CA-AKI + Fasudil (n = 24). All animals underwent two mpMRI studies (arterial spin labeling, T1 and T2 mapping) at baseline and post iopromide/fasudil injection (Days 1, 3, 7, and 13 respectively). Relative change in renal blood flow (ΔRBF), T1 (ΔT1) and T2 (ΔT2) values were assessed at specified time points. Serum levels of cystatin C (CysC) and interleukin-1β (IL-1β), and urinary neutrophil gelatinase-associated lipocalin (NGAL) concentrations were tested as laboratory biomarkers, in addition to examining renal histology and expression levels of various proteins (Rho-kinase [ROCK], α-smooth muscle actin [α-SMA]), hypoxia-inducible factor-1α (HIF-1α), and transforming growth factor-β1 (TGF-β1) that regulate renal fibrosis and hypoxia. Results: Compared with the control group, serum levels of CysC and IL-1β, and urinary NGAL concentrations were clearly increased from Day 1 to Day 13 in the CA-AKI group (all p < 0.05). There were significant reductions in ΔT2 values on Days 1 and 3, and ΔT1 reductions were significantly more pronounced at all time points (Days 1–13) in the CA-AKI + Fasudil group (vs. CA-AKI) (all p < 0.05). Fasudil treatment lowered expression levels of ROCK-1, and p-MYPT1/MYPT1 proteins induced by iopromide, decreasing TGF-β1 expression and suppressing both extracellular matrix accumulation and α-SMA expression relative to untreated status (all p < 0.05). Fasudil also enhanced PHD2 transcription and inhibition of HIF-1α expression after CA-AKI. Conclusions: In the context of CA-AKI, fasudil appears to reduce renal hypoxia, fibrosis, and dysfunction by activating (Rho/ROCK) or inhibiting (TGF-β1, HIF-1α) certain signaling pathways and reducing α-SMA expression. Multiparametric MRI may be a viable noninvasive tool for monitoring CA-AKI pathophysiology during fasudil therapy. Frontiers Media S.A. 2022-06-15 /pmc/articles/PMC9242620/ /pubmed/35784704 http://dx.doi.org/10.3389/fphar.2022.905547 Text en Copyright © 2022 Wang, Wang, Tan, Guo, Chen, Wu, Wang and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wang, Bin
Wang, Yongfang
Tan, Yan
Guo, Jinxia
Chen, Haoyuan
Wu, Pu-Yeh
Wang, Xiaochun
Zhang, Hui
Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI
title Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI
title_full Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI
title_fullStr Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI
title_full_unstemmed Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI
title_short Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI
title_sort assessment of fasudil on contrast-associated acute kidney injury using multiparametric renal mri
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242620/
https://www.ncbi.nlm.nih.gov/pubmed/35784704
http://dx.doi.org/10.3389/fphar.2022.905547
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