title: Irinotecan injures tight junction and causes bacterial translocation in rat.
abstract: BACKGROUND
  Tight junctions are an essential component of intestinal epithelial barriers. Claudin-1, occludin, and ZO-1 are the components of tight junction. The purpose of this study was to investigate whether irinotecan induces bacterial translocation in rats, and thus elucidate the relationship between tight junction and bacterial translocation.
  
  
  METHODS
  Ten rats were divided into two groups: Five were treated with irinotecan and five were not treated with irinotecan, the control group. Irinotecan treated rats were administrated irinotecan 250 mg/kg intraperitoneally on days designated 0 and 1, were then killed at 48 h after treatment, and tissues were collected for analysis. Controls were treated with a saline solution.
  
  
  RESULTS
  In eighty percent of irinotecan treated rats, bacteria were detected in the mesenteric lymph node or spleen. Large intestinal resistance of the rats was decreased. On the contrary, small intestinal resistance increased. Claudin-1 protein expression of both the small and large intestine decreased (P < 0.05), occludin protein expression of the small intestine decreased (P < 0.05), and occludin protein expression of the large intestine had decreasing tendency (P = 0.07) in irinotecan treated rats. In irinotecan treated rats, claudin-1 mRNA of the small intestine decreased (P < 0.05), claudin-1 mRNA of large intestine had a tendency to decrease (P = 0.05), occludin mRNA of both small and large intestine decreased (P < 0.05).
  
  
  CONCLUSIONS
  Irinotecan injures claudin-1 and occludin. It causes disorders in the intestinal epithelial barrier and induces bacterial translocation.
authors.affiliation: Department of Surgery, Institute of Health Bioscience, University of Tokushima, Tokushima, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakao
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kurita
authors.forename: Masato
authors.initials: M
authors.lastname: Komatsu
authors.forename: Kozo
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Toru
authors.initials: T
authors.lastname: Utusnomiya
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D018988:Bacterial Translocation / Q000187:drug effects*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D062445:Claudin-1; D003967:Diarrhea / Q000139:chemically induced; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D000077146:Irinotecan; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010539:Permeability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000187:drug effects*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D062445:Claudin-1; C568114:Cldn1 protein, rat; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D012333:RNA, Messenger; D000077146:Irinotecan; D002166:Camptothecin