title: Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Diao
authors.forename: Qiao
authors.initials: Q
authors.lastname: Mei
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Xu
authors.forename: Xiao-Chang
authors.initials: XC
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Juan
authors.initials: J
authors.lastname: Jin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yao
authors.forename: Mo-Li
authors.initials: ML
authors.lastname: Chen
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D010539:Permeability; D015363:Quinolones / Q000494:pharmacology*; D011897:Random Allocation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015363:Quinolones; D009243:NAD; D004008:Diclofenac; C052785:rebamipide; D000409:Alanine