The mycotoxin patulin increases colonic epithelial permeability in vitro.
The gastrointestinal lumen is directly exposed to dietary contaminants, including patulin, a mycotoxin produced by moulds. Patulin is known to increase permeability across intestinal Caco-2 monolayers. This study aimed to determine the effect of patulin on permeability, ion transport and morphology in isolated rat colonic mucosae. Mucosal sheets were mounted in Ussing chambers and voltage clamped. Apical addition of patulin (100-500 μM) rapidly reduced transepithelial electrical resistance (TEER) and increased permeability to [(14)C] mannitol (2.9-fold). Patulin also inhibited carbachol-induced electrogenic chloride secretion and histological evidence of mucosal damage was observed. To examine potential mechanisms of action of patulin on colonic epithelial cells, high-content analysis of Caco-2 cells was performed and this novel, quantitative fluorescence-based approach confirmed its cytotoxic effects. With regard to time course, the cytotoxicity determined by high content analysis took longer than the almost immediate reduction of electrical resistance in isolated mucosal sheets. These data indicate patulin is not only cytotoxic to enterocytes but also has the capacity to directly alter permeability and ion transport in intact intestinal mucosae. These data corroborate and extend findings in intestinal cell culture monolayers, and further suggest that safety limits on consumption of patulin may be warranted.
UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
H M
HM
Mohan
D
D
Collins
S
S
Maher
E G
EG
Walsh
D C
DC
Winter
P J
PJ
O'Brien
D J
DJ
Brayden
A W
AW
Baird
D000818:Animals; D018938:Caco-2 Cells / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D017136:Ion Transport; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010365:Patulin / Q000493:pharmacokinetics* / Q000633:toxicity*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D008353:Mannitol; D010365:Patulin