Pharmacological reports : PR · 2026
Pre-treatment with 2-mercaptoethanol attenuates ferroptosis-associated redox imbalance and inflammatory responses, but not tubulointerstitial fibrosis, in unilateral ureteral obstruction.
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Moon Daeun, Kim Jinu
Аннотация
BACKGROUND: Unilateral ureteral obstruction (UUO) induces oxidative stress, inflammation, ferroptosis, and progressive fibrotic remodeling. Whether pharmacological modulation of ferroptosis-related redox imbalance attenuates obstructive kidney injury remains unclear. In this study, we investigated the effects of the thiol-containing antioxidant 2-mercaptoethanol (2-ME) in a mouse UUO model.
METHODS: Mice subjected to UUO received either pre-treatment or delayed treatment with 2-ME. Ferroptosis-related markers, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), the ratio of reduced to oxidized glutathione (GSH/GSSG), and lipid hydroperoxides, as well as inflammatory mediators, F4/80-positive macrophage infiltration, Havcr1 mRNA expression, and fibrotic parameters were evaluated using molecular and histological analyses.
RESULTS: UUO markedly decreased the expression of GPX4 and SLC7A11, reduced the GSH/GSSG ratio, and elevated lipid hydroperoxide levels. These changes were accompanied by increased tubular injury scores, infiltration of F4/80-positive macrophages, and extracellular matrix accumulation. Pre-treatment with 2-ME increased GPX4 and SLC7A11 expression, improved the GSH/GSSG balance, reduced lipid hydroperoxide levels, and attenuated inflammatory activation. Additionally, 2-ME pre-treatment significantly reduced tubular injury scores and Havcr1 mRNA expression. However, 2-ME did not consistently suppress collagen deposition or the expression of fibrosis-related genes. Delayed administration of 2-ME failed to significantly alter antioxidant, inflammatory, or fibrotic markers.
CONCLUSIONS: Pre-treatment with 2-ME attenuates ferroptosis-associated redox imbalance and inflammatory responses in UUO but does not consistently suppress tubulointerstitial fibrosis. These findings suggest that 2-ME can serve as a pharmacological tool to modulate thiol-dependent redox balance and inflammatory activation during UUO, whereas fibrosis progression likely involves additional mechanisms.
CLINICAL TRIAL NUMBER: Not applicable.
METHODS: Mice subjected to UUO received either pre-treatment or delayed treatment with 2-ME. Ferroptosis-related markers, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), the ratio of reduced to oxidized glutathione (GSH/GSSG), and lipid hydroperoxides, as well as inflammatory mediators, F4/80-positive macrophage infiltration, Havcr1 mRNA expression, and fibrotic parameters were evaluated using molecular and histological analyses.
RESULTS: UUO markedly decreased the expression of GPX4 and SLC7A11, reduced the GSH/GSSG ratio, and elevated lipid hydroperoxide levels. These changes were accompanied by increased tubular injury scores, infiltration of F4/80-positive macrophages, and extracellular matrix accumulation. Pre-treatment with 2-ME increased GPX4 and SLC7A11 expression, improved the GSH/GSSG balance, reduced lipid hydroperoxide levels, and attenuated inflammatory activation. Additionally, 2-ME pre-treatment significantly reduced tubular injury scores and Havcr1 mRNA expression. However, 2-ME did not consistently suppress collagen deposition or the expression of fibrosis-related genes. Delayed administration of 2-ME failed to significantly alter antioxidant, inflammatory, or fibrotic markers.
CONCLUSIONS: Pre-treatment with 2-ME attenuates ferroptosis-associated redox imbalance and inflammatory responses in UUO but does not consistently suppress tubulointerstitial fibrosis. These findings suggest that 2-ME can serve as a pharmacological tool to modulate thiol-dependent redox balance and inflammatory activation during UUO, whereas fibrosis progression likely involves additional mechanisms.
CLINICAL TRIAL NUMBER: Not applicable.