Metformin ameliorates Gestational Diabetes Mellitus via inhibiting ferroptosis of trophoblasts through the Nrf2/HO-1 signaling pathway DOI

Lingya Fang,

Sha Lu,

Liuyuan Fang

et al.

Free Radical Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: Feb. 17, 2025

Both mothers and infants experience oxidative stress due to gestational diabetes mellitus (GDM), which is strongly associated with adverse pregnancy outcomes. Ferroptosis, a novel form of programmed cell death characterized by iron-dependent lipid peroxidation, believed play critical role in the pathogenesis progression GDM. Metformin (MET) has shown potential alleviating stress; however, research on its specific mechanisms action GDM remains limited. We collected placental tissues from patients healthy controls established an vitro model. measured markers ferroptosis including malondialdehyde (MDA), glutathione (GSH), peroxidase 4 (GPX4) activity. Additionally, we evaluated reactive oxygen species (ROS) levels, apoptosis, viability, migration Our findings revealed significant changes group compared controls, increased MDA GSSG decreased GSH reduced expression GPX4 protein placenta. High-glucose (HG) conditions were reduce trophoblast viability migration, accompanied elevated ROS as well GSH, GPX4, Nrf2, HO-1 proteins. Importantly, treatment MET reversed these effects, similar deferoxamine mesylate (DFOM), known inhibitor. These results confirm occurrence placentas demonstrate that mitigates high-glucose-induced trophoblasts through Nrf2/HO-1 signaling pathway. This study provides insights into protective MET, offering therapeutic strategies for management.

Language: Английский

Metformin ameliorates Gestational Diabetes Mellitus via inhibiting ferroptosis of trophoblasts through the Nrf2/HO-1 signaling pathway DOI

Lingya Fang,

Sha Lu,

Liuyuan Fang

et al.

Free Radical Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: Feb. 17, 2025

Both mothers and infants experience oxidative stress due to gestational diabetes mellitus (GDM), which is strongly associated with adverse pregnancy outcomes. Ferroptosis, a novel form of programmed cell death characterized by iron-dependent lipid peroxidation, believed play critical role in the pathogenesis progression GDM. Metformin (MET) has shown potential alleviating stress; however, research on its specific mechanisms action GDM remains limited. We collected placental tissues from patients healthy controls established an vitro model. measured markers ferroptosis including malondialdehyde (MDA), glutathione (GSH), peroxidase 4 (GPX4) activity. Additionally, we evaluated reactive oxygen species (ROS) levels, apoptosis, viability, migration Our findings revealed significant changes group compared controls, increased MDA GSSG decreased GSH reduced expression GPX4 protein placenta. High-glucose (HG) conditions were reduce trophoblast viability migration, accompanied elevated ROS as well GSH, GPX4, Nrf2, HO-1 proteins. Importantly, treatment MET reversed these effects, similar deferoxamine mesylate (DFOM), known inhibitor. These results confirm occurrence placentas demonstrate that mitigates high-glucose-induced trophoblasts through Nrf2/HO-1 signaling pathway. This study provides insights into protective MET, offering therapeutic strategies for management.

Language: Английский

Citations

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