Morphological and functional recovery following exposure to deoxycholic acid

Abstract

Whereas many studies deal with teh deleterious effects of unconjugated deoxycholic acid on epithelial morphology, few are concerned with the reversibility of these effects, the subject of the present study. Tied jejunal loops in the rat were incubated for 30 minutes with deoxycholic acid (2.5-20 mmol/litre) in isotonic solution. Immediately after this treatment, or after a subsequent recovery period of 15 or 150 minutes following wash out of the bile acid, the loops were excised, fixed and examined by light microscopy and scanning electron microscopy. Deoxycholic acid produced epithelial lesions whose severity and reversibility depended on the concentration applied. However, even the severely affected epithelium obtained by treatment at 10-20 mmol/litre was reverted to normal within 150 minutes, and a substantial normalisation was observed already after 15 minutes. An exception to this rapid restoration of epithelial morphology and integrity was noted in villi which had suffered necrosis of lamina propria. The revertion of epithelial pathology was paralleled with a normalisation of glucose absorption, of the potassium ion and protein content of the loop fluid, and of the paracellular epithelial permeability as measured with 3-H-poly-ethylenglycol. Morphometry showed that deoxycholic acid caused villous atrophy without affectin the crypt length. The extent and reversibility of this atrophy depended on dose and recovery time as above. It is suggested that the remarkably fast morphological restitution proceeds mainly by process involving cellular remodelling and migration.