Effect of Shiga-like toxin II from Escherichia coli O157:H7 on intestinal clearance of norfloxacin in rats.
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.
Nakayama
Hironao
H
Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Nagoya 461-8763, Japan.
Kitaichi
Kiyoyuki
K
Kanazawa
Hiroaki
H
Ando
Mai
M
Fujimoto
Yohei
Y
Takagi
Kenji
K
Takagi
Kenzo
K
Hasegawa
Takaaki
T
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
D000890:Anti-Infective Agents; D022641:Shiga Toxin 2; D009643:Norfloxacin; D002331:Carnitine