Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation

• Published in: Toxicology (Amsterdam) Vol. 304; pp. 41 - 48
• Main Authors: Wu, Hai-Lu, Gao, Xin, Jiang, Zong-Dan, Duan, Zhao-Tao, Wang, Shu-Kui, He, Bang-Shun, Zhang, Zhen-Yu, Xie, Hong-Guang
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 08.02.2013
• Subjects: Adverse drug reaction; apoptosis; Apoptosis - drug effects; Blotting, Western; Cell Line; cell proliferation; Cell Proliferation - drug effects; cell viability; Clopidogrel; dextran; Dose-Response Relationship, Drug; Emergency; epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - pathology; Extracellular Signal-Regulated MAP Kinases - metabolism; Flow Cytometry; Gastric injury; Gastric Mucosa - drug effects; Gastric Mucosa - pathology; Gene Expression Regulation - drug effects; GES-1 cell line; hemorrhage; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; Microscopy, Electron, Transmission; mitogen-activated protein kinase; Occludin - genetics; occludins; p38 MAPK; p38 Mitogen-Activated Protein Kinases - metabolism; permeability; phosphorylation; Phosphorylation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - toxicity; signal transduction; Signal Transduction - drug effects; stomach ulcers; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Ticlopidine - toxicity; Tight junction protein; tight junctions; Tight Junctions - drug effects; Tight Junctions - metabolism; Toxicology; transmission electron microscopy; Western blotting; Zonula Occludens-1 Protein - genetics; extracellular signal-regulated kinase; zona occludens 1; Gastric injury; DMSO; JNK; Adverse drug reaction; the concentration required to achieve one-half the maximal inhibition; MTT; GES-1; SB-203580; Toxicology; MDCK; fluorescein isothiocyanate; PBS; c-Jun N-terminal kinase; MVEC; DAPI; 4′,6-diamidino-2-phenylindole; MAPK; ERK inhibitor; Tight junction protein; p38 MAPK; p38 MAPK inhibitor; gastrointestinal; immortalized human gastric epithelial cells line; Hank's Balanced Salt Solution; T-84; ZO-1; human colorectal carcinoma cell line; ERK; IC 50; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; p38 mitogen-activated protein kinases; SP-600125; GES-1 cell line; FITC; dimethyl sulfoxide; p38; tight junction; U-0126; GI; microvascular endothelial cells; junction adhesion molecule; mitogen-activated protein kinases; Madin–Darby canine kidney cell line; phosphate buffered saline; TJ; JAM; Clopidogrel; HBSS; JNK inhibitor; IC50
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2012.11.020

Highlights ► Clopidogrel suppressed GES-1 cell viability in a concentration- and time-dependent manner. ► Clopidogrel significantly increased dextran permeability, reduced occludin and ZO-1 expression, and induced cell apoptosis. ► Clopidogrel activated p38 MAPK signaling pathway. ► Activation of p38 activity was involved in clopidogrel-induced increase in gastric epithelial cells permeability and disruption of TJ.