Key result
Clopidogrel induces gastric mucosal injury and apoptosis in rats and human cells via increased ER stress.
Why the study?
Clopidogrel use is limited by gastrointestinal adverse effects such as gastric mucosal injury, prompting investigation into whether this injury involves ER stress- and apoptosis-related markers.
Does clopidogrel induce gastric mucosal injury through ER stress and apoptosis in preclinical models?
Does clopidogrel induce gastric mucosal injury through ER stress and apoptosis in preclinical models?
Clopidogrel-induced gastric mucosal injury is associated with increased ER stress and apoptosis in preclinical models, providing mechanistic insight into its gastrointestinal adverse effects.
May implicate ER stress in clopidogrel gastric injury; hypothesis-generating in animal models and requires human validation.
Clopidogrel is widely used as an antiplatelet agent for the prevention and treatment of arterial thrombotic diseases, but its clinical application may be limited by gastrointestinal adverse effects, including gastric mucosal injury. Because epithelial cell survival is essential for maintaining gastric mucosal integrity, we hypothesized that clopidogrel-induced gastric epithelial injury would be accompanied by alterations in ER stress- and apoptosis-related markers. To test this hypothesis, GES-1 human gastric epithelial cells were treated with different concentrations of clopidogrel, and cell viability, apoptosis, cell cycle distribution, and molecular changes were evaluated using the Cell Counting Kit-8 (CCK-8) assay, flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. In parallel, Sprague-Dawley rats were administered clopidogrel by gavage to establish an in vivo gastric injury model. Gastric mucosal pathological changes were assessed by hematoxylin and eosin staining, and serum inflammatory cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA). Clopidogrel reduced GES-1 cell viability, promoted apoptosis, and altered cell cycle progression. In rats, clopidogrel induced gastric mucosal erosion, edema, and inflammatory cell infiltration, accompanied by increased serum interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels. Clopidogrel also increased the expression of the ER stress markers C/EBP homologous protein (CHOP) and activating transcription factor 5 (ATF5), increased Bcl-2-associated X protein (Bax) expression, decreased B-cell lymphoma 2 (Bcl-2) expression, and elevated the Bax/Bcl-2 ratio in both gastric tissues and GES-1 cells. These findings suggest that clopidogrel-induced gastric mucosal injury is associated with increased ER stress-related marker expression and disruption of the Bax/Bcl-2 balance, although a direct causal ER stress-mitochondrial apoptosis pathway was not established in this study.
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Li et al. (2026) studied Gastric mucosal injury. Clopidogrel was evaluated on Cell viability, apoptosis, cell cycle distribution, and gastric mucosal pathological changes. Clopidogrel induced gastric mucosal injury and apoptosis in rats and human gastric epithelial cells, associated with increased ER stress markers and an elevated Bax/Bcl-2 ratio.
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