Acute Effects of Topical Methyl Tert–Butyl Ether or Ethyl Propionate on Gallbladder Histology in Animals: A Comparison of Two Solvents for Contact Dissolution of Cholesterol Gallstones

Abstract

Experiments were performed in anesthetized rabbits and piglets to assess gallbladder mucosal injury during irrigation with methyl tert-butyl ether, a C5 ether, or ethyl propionate, a C5 ester--two organic solvents used in the contact dissolution of cholesterol gallstones. In 44 New Zealand White rabbits, the gallbladder was exposed to individual solvents or saline solution through a transhepatic catheter for 2 hr. Gallbladders were then harvested and fixed immediately or after a recovery period of 1, 4 or 8 days. Tissue sections were examined under light microscopy, and severity of injury was graded with predefined criteria by two pathologists blinded to the animals' treatment regimens. Histological assessment showed severe mucosal injury such as necrosis of the cells at the villus tips immediately after 2 hr of exposure to either solvent. After 4 days, injury had decreased significantly; after 8 days, complete mucosal healing had taken place. A similar study was performed in 32 piglets. Solvent or saline solution was oscillated in and out of the gallbladders of these piglets with a computer-controlled syringe pump at a pressure less than the leakage pressure of the gallbladder. Histological assessment was performed on tissue samples obtained immediately after the procedure or 8 days later. Both solvents caused severe mucosal injury; however, after 8 days complete mucosal healing had occurred, so that gallbladders exposed to solvent were indistinguishable from gallbladders exposed to saline solution, which was used as control. We conclude that both methyl tert-butyl ether and ethyl propionate cause moderate to severe epithelial injury but that the gallbladder epithelium regenerates within a few days.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile acids: Trying to understand their chemistry and biology with the hope of helping patients #

“…Studies in pigs conducted by Oliver Esch in our laboratory indicated that the gallbladder epithelium was completely destroyed by MTBE, but quickly regenerated. 112 In our laboratory in San Diego, Salam Zakko, a fellow with remarkable talents in electronics, developed a highly intelligent pump capable of inducing turbulent flow around the gallstone; a pressure sensor that fed back on the inflow and outflow pumps kept the solvent in the gallbladder even if there was gallbladder contraction. 113,114 We found that ethyl propionate (a C 5 ester) dissolved gallstones in vitro as rapidly as MTBE (a C 5 ether), and was much better tolerated by the patient because of its lower volatility and rapid metabolism.…”

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

“…The procedure required some hours for complete dissolution, and as described, it required professional personnel to perform the infusion and aspiration . In studies performed in pigs, the gallbladder epithelium was observed to be destroyed by either solvent, although it recovered rapidly ( 443 ). There There is still much is to be learned about the effect of individual bile acids on the microbiome ( 465 ).…”

The Cumulative Risk Assessment of Hepatotoxic Chemicals: A Hepatic Histopathology Perspective

“…47,50,51 The industrial chemical intermediate, dibutyltin dichloride, has been used as a model for the induction of acute pancreatitis in laboratory rodents, but which also induces a primary biliary mucosal necrosis of the common bile duct and larger interlobular ducts of the liver. [52][53][54][55] The necrosis of the epithelial cells is followed by a series of secondary pathological changes such as submucosal edema, extrahepatic cholestasis, and inflammation both within the affected tissues and throughout the periportal regions of the liver lobules. Serum bilirubin, ALP, GGT, and ALT are frequently elevated due to the secondary effects on the liver 56 but are not pathognomonic of primary biliary toxicity.…”