title: Effect of Shiga-like toxin II from Escherichia coli O157:H7 on intestinal clearance of norfloxacin in rats.
abstract: Enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection causes severe clinical symptoms, due to its bacterial toxin, called Shiga-like toxin (SLT). However, little is known about the information to establish a safe and efficient prescription to treat for EHEC O157:H7 patients. Thus, we investigated the effect of SLT-II on intestinal function in rats by using the antibiotic norfloxacin (NFLX) as a model drug. The intestinal clearance (CLi) of NFLX, determined by loop method in the jejunum, was significantly decreased by SLT-II. In histopathological experiment, epithalaxia was observed in SLT-II-treated rats without structural changes of tight junction suggesting the deterioration of active transport systems by SLT-II. CLi of NFLX in normal rats was decreased by carnitine (CAR), suggesting the possible involvement of CAR-sensitive transporter in CLi of NFLX. Taken together, these results suggest that the EHEC O157:H7 infection might affect the intestinal disposition of NFLX due to the changing intestinal expression/function of drug transporters by SLT-II.
authors.affiliation: Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Nagoya 461-8763, Japan.
authors.forename: Hironao
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Kitaichi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Mai
authors.initials: M
authors.lastname: Ando
authors.forename: Yohei
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagi
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takagi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001692:Biological Transport; D002331:Carnitine / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D004926:Escherichia coli / Q000737:chemistry*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009643:Norfloxacin / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022641:Shiga Toxin 2 / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D000890:Anti-Infective Agents; D022641:Shiga Toxin 2; D009643:Norfloxacin; D002331:Carnitine