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Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation

Chronic kidney disease (CKD) is a kidney structure and function abnormality. CKD development and progression are strongly influenced by oxidative stress and inflammatory responses, which can lead to tubulointerstitial fibrosis. Unfortunately, there are no effective or specific treatments for CKD. We...

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Autores principales: Kim, Jeongwon, Lee, Jieun, Yoon, Dahye, Son, Minjung, Kim, Mi-Jeong, Ha, Sugyeong, Kim, Doyeon, Yoo, Ji-an, Kim, Donghwan, Chung, Hae Young, Moon, Hyung Ryong, Chung, Ki Wung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10669799/
https://www.ncbi.nlm.nih.gov/pubmed/38001800
http://dx.doi.org/10.3390/antiox12111947
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author Kim, Jeongwon
Lee, Jieun
Yoon, Dahye
Son, Minjung
Kim, Mi-Jeong
Ha, Sugyeong
Kim, Doyeon
Yoo, Ji-an
Kim, Donghwan
Chung, Hae Young
Moon, Hyung Ryong
Chung, Ki Wung
author_facet Kim, Jeongwon
Lee, Jieun
Yoon, Dahye
Son, Minjung
Kim, Mi-Jeong
Ha, Sugyeong
Kim, Doyeon
Yoo, Ji-an
Kim, Donghwan
Chung, Hae Young
Moon, Hyung Ryong
Chung, Ki Wung
author_sort Kim, Jeongwon
collection PubMed
description Chronic kidney disease (CKD) is a kidney structure and function abnormality. CKD development and progression are strongly influenced by oxidative stress and inflammatory responses, which can lead to tubulointerstitial fibrosis. Unfortunately, there are no effective or specific treatments for CKD. We investigated the potential of the thiobarbiturate-derived compound MHY1025 to alleviate CKD by reducing oxidative stress and inflammatory responses. In vitro experiments using NRK52E renal tubular epithelial cells revealed that MHY1025 significantly reduced LPS-induced oxidative stress and inhibited the activation of the NF-κB pathway, which is involved in inflammatory responses. Furthermore, treatment with MHY1025 significantly suppressed the expression of fibrosis-related genes and proteins induced by TGFβ in NRK49F fibroblasts. Furthermore, we analyzed the MHY1025 effects in vivo. To induce kidney fibrosis, mice were administered 250 mg/kg folic acid (FA) and orally treated with MHY1025 (0.5 mg/kg/day) for one week. MHY1025 effectively decreased the FA-induced inflammatory response in the kidneys. The group treated with MHY1025 exhibited a significant reduction in cytokine and chemokine expression and decreased immune cell marker expression. Decreased inflammatory response was associated with decreased tubulointerstitial fibrosis. Overall, MHY1025 alleviated renal fibrosis by directly modulating renal epithelial inflammation and fibroblast activation, suggesting that MHY1025 has the potential to be a therapeutic agent for CKD.
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spelling pubmed-106697992023-10-31 Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation Kim, Jeongwon Lee, Jieun Yoon, Dahye Son, Minjung Kim, Mi-Jeong Ha, Sugyeong Kim, Doyeon Yoo, Ji-an Kim, Donghwan Chung, Hae Young Moon, Hyung Ryong Chung, Ki Wung Antioxidants (Basel) Article Chronic kidney disease (CKD) is a kidney structure and function abnormality. CKD development and progression are strongly influenced by oxidative stress and inflammatory responses, which can lead to tubulointerstitial fibrosis. Unfortunately, there are no effective or specific treatments for CKD. We investigated the potential of the thiobarbiturate-derived compound MHY1025 to alleviate CKD by reducing oxidative stress and inflammatory responses. In vitro experiments using NRK52E renal tubular epithelial cells revealed that MHY1025 significantly reduced LPS-induced oxidative stress and inhibited the activation of the NF-κB pathway, which is involved in inflammatory responses. Furthermore, treatment with MHY1025 significantly suppressed the expression of fibrosis-related genes and proteins induced by TGFβ in NRK49F fibroblasts. Furthermore, we analyzed the MHY1025 effects in vivo. To induce kidney fibrosis, mice were administered 250 mg/kg folic acid (FA) and orally treated with MHY1025 (0.5 mg/kg/day) for one week. MHY1025 effectively decreased the FA-induced inflammatory response in the kidneys. The group treated with MHY1025 exhibited a significant reduction in cytokine and chemokine expression and decreased immune cell marker expression. Decreased inflammatory response was associated with decreased tubulointerstitial fibrosis. Overall, MHY1025 alleviated renal fibrosis by directly modulating renal epithelial inflammation and fibroblast activation, suggesting that MHY1025 has the potential to be a therapeutic agent for CKD. MDPI 2023-10-31 /pmc/articles/PMC10669799/ /pubmed/38001800 http://dx.doi.org/10.3390/antiox12111947 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Jeongwon
Lee, Jieun
Yoon, Dahye
Son, Minjung
Kim, Mi-Jeong
Ha, Sugyeong
Kim, Doyeon
Yoo, Ji-an
Kim, Donghwan
Chung, Hae Young
Moon, Hyung Ryong
Chung, Ki Wung
Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation
title Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation
title_full Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation
title_fullStr Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation
title_full_unstemmed Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation
title_short Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation
title_sort thiobarbiturate-derived compound mhy1025 alleviates renal fibrosis by modulating oxidative stress, epithelial inflammation, and fibroblast activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10669799/
https://www.ncbi.nlm.nih.gov/pubmed/38001800
http://dx.doi.org/10.3390/antiox12111947
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