title: Intestinal permeability to iohexol as an in vivo marker of chemotherapy-induced gastrointestinal toxicity in Sprague-Dawley rats.
abstract: Gastrointestinal toxicity is the most common adverse effect of chemotherapy. Chemotherapeutic drugs damage the intestinal mucosa and increase intestinal permeability. Intestinal permeability is one of the key markers of gastrointestinal function and measuring intestinal permeability could serve as a useful tool for assessing the severity of chemotherapy-induced gastrointestinal toxicity.
  
  
  
  Male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg) or irinotecan (200 mg/kg). Clinical signs of gastrointestinal toxicity were assessed daily by weighing the animals and by checking for diarrhea. After 48 h, intestinal permeability to iohexol was measured in vivo by giving the animals 1 ml of 647 mg/ml iohexol solution by oral gavage and collecting all the excreted urine for 24 h. All of the animals were euthanized 72 h after drug administration and tissue samples were harvested from the jejunum and colon.
  
  
  
  All chemotherapeutics caused significant body weight loss and diarrhea. Intestinal permeability to iohexol was also increased in all treatment groups and histological analysis revealed significant intestinal damage in both jejunum and colon. Iohexol permeability correlated with the severity of clinical signs of gastrointestinal toxicity and with acute colonic injury.
  
  
  
  Chemotherapeutic drugs, such as 5-fluorouracil, oxaliplatin, and irinotecan, increase intestinal permeability to iohexol. Measuring intestinal permeability to iohexol could provide a simple marker for assessing chemotherapy-induced gastrointestinal toxicity.
authors: Pharmacology, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland. richard.forsgard@helsinki.fi.
authors: Richard A
authors: RA
authors: Forsgård
authors: Pharmacology, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland.
authors: Riitta
authors: R
authors: Korpela
authors: Pharmacology, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland.
authors: Reetta
authors: R
authors: Holma
authors: Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
authors: Jere
authors: J
authors: Lindén
authors: Central Animal Laboratory, University of Turku, Turku, Finland.|Comparative Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Rafael
authors: R
authors: Frias
authors: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
authors: Thomas
authors: T
authors: Spillmann
authors: Department of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Pia
authors: P
authors: Österlund
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D000970:Antineoplastic Agents / Q000633:toxicity*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D001835:Body Weight; D002166:Camptothecin / Q000031:analogs & derivatives / Q000633:toxicity; D002772:Cholera Toxin / Q000097:blood; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media / Q000493:pharmacokinetics*; D003967:Diarrhea / Q000139:chemically induced; D005472:Fluorouracil / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D006242:Haptoglobins; D007413:Intestinal Mucosa / Q000187:drug effects; D007472:Iohexol / Q000493:pharmacokinetics*; D000077146:Irinotecan; D007583:Jejunum / Q000378:metabolism / Q000473:pathology; D008297:Male; D009944:Organoplatinum Compounds / Q000633:toxicity; D000077150:Oxaliplatin; D010539:Permeability; D011498:Protein Precursors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D006242:Haptoglobins; D009944:Organoplatinum Compounds; D011498:Protein Precursors; C408043:zonulin; D000077150:Oxaliplatin; D007472:Iohexol; D000077146:Irinotecan; D002772:Cholera Toxin; D005472:Fluorouracil; D002166:Camptothecin
keywords: 5-Fluorouracil; Chemotherapy; Intestinal permeability; Irinotecan; Oxaliplatin