Disruption of colonic electrolyte transport in experimental colitis

Abstract

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.

Effect of quercitrin on the early stages of hapten induced colonic inflammation in the rat

“…The dramatic increase in tissue conductance, the extremely low voltage, the lack of response to carbachol and the macroscopic appearance all indicate epithelial necrosis of the distal colon. This is in agreement with previous reports [4,5,11]. The fact that basal Isc in this segment was normal can be easily explained because both tissue conductance and voltage were shifted by approximately 10-fold, so that the resultant Isc would be roughly unchanged, according to Ohm's law (I = V Â G).…”

“…The colonic segments were placed on an ice-cold plate, cleaned of fat and mesentery, and blotted on filter paper. The colon was cut longitudinally and scored for visible damage according to the criterion of Bell et al [11]. The colon was subsequently divided in proximal and distal segments, each one of which was longitudinally cut into several fragments.…”

T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase

“…These data also indicated that tissue inflammation was associated with decreased Na + absorption. In animal models of colitis, both hyporesponsiveness to secretagogues (45) and decreased Na + -absorptive processes (Na + -dependent glucose absorption and non-nutrient-dependent Na + and Cl -transport) have been observed (46,47). Similar to the present findings, decreased Na + /K + -ATPase activity was measured in inflamed intestine (48).…”

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

“…They were placed on an ice-cold plate, cleaned of fat and mesentery, and blotted on filter paper, and the colon was weighed and its length measured under a constant load (2 g). The colon was longitudinally opened and scored for macroscopically visible damage on a 0-10 scale by two observers unaware of the treatment, according to the criteria described by Bell et al 19) ( Table 1). The colon was subsequently divided longitudinally into different pieces to be used for the biochemical determinations: myeloperoxidase (MPO) activity, alkaline phosphatase (AP) activity and total glutathione (GSH) content.…”