Original Article
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World J Gastroenterol. Mar 14, 2012; 18(10): 1059-1066
Published online Mar 14, 2012. doi: 10.3748/wjg.v18.i10.1059
Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice
Lei Diao, Qiao Mei, Jian-Ming Xu, Xiao-Chang Liu, Jing Hu, Juan Jin, Qiang Yao, Mo-Li Chen
Lei Diao, Qiao Mei, Jian-Ming Xu, Xiao-Chang Liu, Jing Hu, Juan Jin, Qiang Yao, Mo-Li Chen, Department of Gastroenterology in the First Affiliated Hospital of Anhui Medical University, the Key Laboratory of Digestive Diseases of Anhui Province, Hefei 230022, Anhui Province, China
Author contributions: Mei Q, Xu JM designed the experiment and were involved in editing the manuscript. Mei Q, Liu XC, Hu J, Jin J, Yao Q, Chen ML performed the experiments, of which the majority were performed by Diao L.
Correspondence to: Qiao Mei, MD, Department of Gastroenterology in the First Affiliated Hospital of Anhui Medical University, the Key Laboratory of Digestive Diseases of Anhui Province, JiXi Road 218, Hefei 230022, Anhui Province, China. meiqiaomq@yahoo.com.cn
Telephone: +86-551-2922039 Fax: +86-551-3633742
Received: June 2, 2011
Revised: June 22, 2011
Accepted: July 8, 2011
Published online: March 14, 2012
Abstract

AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice.

METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity.

RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling.

CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

Keywords: Intestinal mucosal permeability; Mitochondria; Non-steroid anti-inflammatory drugs; Oxidative damage; Rebamipide; Tight junction