Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice  

作　　者：Lei Diao Qiao Mei Jian-Ming Xu Xiao-Chang Liu Jing Hu Juan Jin Qiang Yao Mo-Li Chen 

机构地区：[1]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

出　　处：《World Journal of Gastroenterology》2012年第10期1059-1066,共8页世界胃肠病学杂志（英文版）

摘　　要：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.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.

关 键 词：Intestinal mucosal permeability MITOCHONDRIA Non-steroid anti-inflammatory drugs Oxidative damage REBAMIPIDE Tight junction 

分 类 号：Q244[生物学—细胞生物学] TQ464.7[化学工程—制药化工]