Disruption of colonic electrolyte transport in experimental colitis.
The time course of disturbances of distal colonic electrolyte transport during experimental colitis in rats was compared with changes in the severity of inflammation and epithelial disruption. Colitis was induced by intracolonic administration of trinitrobenzenesulfonic acid (TNBS). At time points from 1 day to 8 wk thereafter, Na+ and Cl- transport was studied under short-circuited conditions in Ussing chambers, three indexes of tissue inflammation were measured, and histology was performed. Net absorption of Na+ and Cl- was abolished at 1 and 4 days after induction of colitis, but recovered to control levels by 1 wk. All unidirectional electrolyte fluxes were elevated at 1 day and fell significantly, generally to control levels, by 4 days. The indexes of inflammation, tissue myeloperoxidase, and synthetic capacities for prostaglandin E2 and leukotriene B4 were all significantly elevated from 1 day to 2 wk post-TNBS. At 1 and 4 days, there was widespread epithelial necrosis, and reepithelialization was consistently seen by 2 wk. In additional studies, 2 wk post-TNBS, the short-circuit current response to 3-isobutyl-1-methylxanthine was reduced compared with controls. These data suggest that abolition of electrolyte absorption early in this experimental colitis was largely attributable to epithelial damage. Despite demonstrable tissue inflammation 2 wk post-TNBS, basal electrolyte transport was not impaired, while the colitic epithelium was hyporesponsive to a Cl- secretagogue. The data also suggest that gross barrier function was restored prior to reepithelialization.
Bell
C J
CJ
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Gall
D G
DG
Wallace
J L
JL
D000818:Animals; D001692:Biological Transport; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015232:Dinoprostone / Q000096:biosynthesis; D004573:Electrolytes / Q000378:metabolism*; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
D004573:Electrolytes; D007975:Leukotriene B4; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D015232:Dinoprostone