TOXIC EFFECTS OF CHOLELITHOLYTIC SOLVENTS ON GALLBLADDER AND LIVER - A PIGLET MODEL STUDY

We evaluated the toxic effects of four currently used chemolytic solve nts-dimethyl sulfoxide (DMSO, 99%), ethyl propionate (EP, 99%), tetras odium ethyl-dimethyl tetraacetate (4Na-EDTA, 2%, pH 11), and methyl te rt-butyl ether (MTBE, purity = 99.5%) in an animal model. Each solvent was tested in nine farm piglets (Landrace), weighing between 20 and 2 5 kg. A solvent-resistant catheter was inserted transhepatically into the gallbladder (GB) using sonographic guidance 24 hr prior to each ex periment. Seventy-five milliliters of each solvent was infused over 3 hr into the gallbladder. The following day, a laparotomy was performed in order to assess for possible damage to the liver, GB, bile ducts ( BD), or intestines. The GB and liver were resected and their histology examined. The following pathologic grades were assigned to GB, BD, an d liver specimens to describe the tissue damage: normal (0), mild (1), moderate (2), and severe (3). We found that DMSO had the highest scor e on gallbladder and bile duct injury (49, 3), followed by EP (36, 2), EDTA (14, 1) and MTBE (16, 0), respectively; the difference in gallbl adder damage was statistically significant. Very mild hepatocyte damag e was present in the DMSO (2) and MTBE (2) groups. The administration of EP and EDTA resulted in no liver injury at all. Piglets within each treatment group suffered from varying degrees of tissue injury. No de aths were attributed to the administered solvents. We concluded that D MSO, EP, EDTA, and MTBE do not have serious local toxic effect on the GB, BD, and intestine; nor do they lead to severe hepatotoxicity. The adverse effects of these solvents depend upon the particular agent use d as well as the inherent susceptibility to toxicity. Hence, if these agents are administered in clinical practice, patients should be monit ored for the possible serious side effects.