A Method to Quantitatively Compare In Vivo the Effects of Gallstone Solvents on Intestinal Mucosal Function: A Controlled Study Comparing Mono-Octanoin with Methyl tert-Butyl Ether in the Rat

Abstract

Abstract

During contact dissolution of gallstones, solvents may escape from the gallbladder and damage the intestinal mucosa. In order to compare the extent of this potential injury, we developed a method to objectively quantify the effects of two commonly used cholesterol solvents, methyl tert-butyl ether and mono-octanoin, on mucosal transport function in the rat intestine.

Two intestinal segments in each of 184 anesthetized rats were cannulated. Three milliliters of either solvent were instilled in one segment and left for varying periods of time, while saline was instilled in the other as control. The segments were then washed and perfused for 45 min with an isotonic solution containing [³H]polyethylene glycol 4000 (a nonabsorbable reference marker) and either [¹⁴C]α-aminoisobutyric acid (a marker for active absorption) or [¹⁴C]mannitol (a marker for passive permeability).

Methyl tert-butyl ether caused more inhibition of α-aminolsobutyric acid absorption (64%) than mono-octanoin (48%) and a greater reduction of dry weight per centimeter of the perfused segment (22%) compared with mono-octanoin (10%). Such effects appeared after only 1 min of solvent exposure and did not appreciably increase with longer exposures. Permeation of mannitol increased by 26% after 1 min of exposure to mono-octanoin and by 54% after a similar period of exposure to methyl tert-butyl ether. Longer exposures to both solvents did not seem to cause progressive increases in mannitol permeation.

The results indicate that brief exposure of the rat jejunum to either of the two solvents causes a reduction in active transport ([¹⁴C]α-aminoisobutyric acid absorption), an increase in passive permeability (mannitol permeation), and a loss of mucosal constituents. We conclude that the intestinal mucosa is susceptible to solvent damage and may be used as a selectively sensitive model that can characterize the biological injury of gallstone solvents. The study also suggests that escape of the currently available solvents into the small intestine in patients undergoing contact dissolution of gallbladder stones may cause injury to the small intestine.