Toxic effects of cholelitholytic solvents on gallbladder and liver - A piglet model study

We evaluated the toxic effects of four currently used chemolytic solvents-dimethyl sulfoxide (DMSO, 99%), ethyl propionate (EP, 99%), tetrasodium ethyl-dimethyl tetraacetate (4Na-EDTA, 2%, pH 11), and methyl tert-butyl ether (MTBE, purity=99.5%) in an animal model. Each solvent was tested in nine farm piglets (Landrace), weighing between 20 and 25 kg. A solvent-resistant catheter was inserted transhepatically into the gallbladder (GB) using sonographic guidance 24 hr prior to each experiment. 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, and liver specimens to describe the tissue damage: normal (0), mild (1), moderate (2), and severe (3). We found that DMSO had the highest score on gallbladder and bile duct injury (49, 3), followed by EP (36, 2), EDTA (14, 1) and MTBE (16, 0), respectively; the difference in gallbladder damage was statistically significant. Very mild hepatocyte damage 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 deaths were attributed to the administered solvents. We concluded that DMSO, 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 used as well as the inherent susceptibility to toxicity. Hence, if these agents are administered in clinical practice, patients should be monitored for the possible serious side effects.