title: 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)
authors.affiliation: Department of Medicine, University of California-San Diego, La Jolla 92093.
authors.forename: O
authors.initials: O
authors.lastname: Esch
authors.forename: J C
authors.initials: JC
authors.lastname: Spinosa
authors.forename: R L
authors.initials: RL
authors.lastname: Hamilton
authors.forename: D L
authors.initials: DL
authors.lastname: Crombie
authors.forename: C D
authors.initials: CD
authors.lastname: Schteingart
authors.forename: J F
authors.initials: JF
authors.lastname: Rondinone
authors.forename: H B
authors.initials: HB
authors.lastname: D'Agostino
authors.forename: J
authors.initials: J
authors.lastname: Lillienau
authors.forename: A F
authors.initials: AF
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D002769:Cholelithiasis / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D004987:Ethers / Q000494:pharmacology*; D005704:Gallbladder / Q000187:drug effects* / Q000473:pathology; D008738:Methyl Ethers; D011422:Propionates / Q000494:pharmacology*; D011817:Rabbits; D012997:Solvents / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors
chemical_list: D004987:Ethers; D008738:Methyl Ethers; D011422:Propionates; D012997:Solvents; C043243:methyl tert-butyl ether; D002784:Cholesterol; C069373:ethyl propionate