Effect of metformin on hepatic ischemia-reperfusion injury-induced endoplasmic reticulum stress: A mechanistic exploration based on molecular docking and experimental validation
Abstract
INTRODUCTION: Hepatic ischemia-reperfusion injury (HIRI) is a major clinical challenge with limited therapeutic options. Metformin (Met) has demonstrated protective effects against ischemia-reperfusion (IR) injury in other organs by modulating endoplasmic reticulum (ER) stress, but its role and mechanism in HIRI remain unclear.
METHODS: A mouse HIRI model was established following Met pre-treatment, with six mice included in each group. HIRI was assessed by measuring serum injury markers, examining histopathological changes, and evaluating apoptosis. ER stress markers were analyzed by western blot. Molecular docking predicted interactions between Met and ER stress proteins. AML12 hepatocytes under hypoxia/reoxygenation (H/R) were treated with Met, VER-155008 (VER), and/or CDN1163, followed by analysis of key cell parameters: viability, lactate dehydrogenase (LDH) release, apoptosis, and calcium flux. In vitro experiments were performed as three independent biological experiments.
RESULTS: Met pre-treatment significantly attenuated IR-induced hepatic injury, evidenced by reduced serum injury markers, histopathological changes, and hepatocyte apoptosis (p < 0.05). Met also suppressed the HIRI-induced upregulation of ER stress proteins, including GRP78, p-PERK, p-IRE1α, and CHOP (p < 0.05). Molecular docking predicted a potential interaction of Met with GRP78. In H/R-induced AML12 hepatocytes, Met, VER, and CDN1163 similarly improved viability and reduced LDH release and…
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.