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

Abstract

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.

• Authors: Jeongwon Kim, Jieun Lee, Dahye Yoon, Minjung Son, Mi-Jeong Kim, Sugyeong Ha, Doyeon Kim, Ji-An Yoo, Donghwan Kim, Hae Young Chung, Hyung Ryong Moon, Ki Wung Chung
• Journal: Antioxidants (Basel, Switzerland) (Antioxidants (Basel)) Vol. 12 Issue 11 (Oct 31 2023) ISSN: 2076-3921 [Print] Switzerland
• PMID: 38001800 (Publication Type: Journal Article)