Superior gallstone dissolubility and safety of tert-amyl ethyl ether over methyl-tertiary butyl ether

Figure 5 Determination of solvent toxicity in the in vivo models of gallstones. A: Cleaved caspase-3 immunohistochemistry of the gallbladder tissues obtained from the hamsters with cholesterol (Top) and pigmented (Bottom) gallstones at 24 h after the intracystic injection of each solvent. Regarding both cholesterol and pigmented gallstones, tert-amyl ethyl ether (TAEE) infusion resulted in significantly lower expression of cleaved caspase-3 than did methyl tert-butyl ether (MTBE) infusion, suggesting a lower toxicity of TAEE compared with MTBE; B: Hematoxylin-eosin stains of the liver and kidney tissues obtained from the hamsters with cholesterol (Left) and pigmented (Right) gallstones at 24 h after the intracystic injection of each solvent. The degree of injury of the liver and kidney were calculated as the Suzuki injury scores and EGTI scores, respectively. Whereas MTBE significantly increased the injuries of the liver and kidney, TAEE did not increase the injuries in both hamster models of cholesterol and pigmented gallstones; C: ELISA results demonstrating the serum levels of pro-inflammatory cytokines, IL-6, and TNF-α in the hamster models of cholesterol (Left) and pigmented (Right) gallstones at 24 h after the intracystic injection of each solvent. In the hamsters with cholesterol gallstones, whereas MTBE significantly increased the serum levels of both IL-6 and TNF-α, TAEE rather decreased the serum levels of the cytokines. In the hamsters with pigmented gallstones, MTBE significantly increased the serum level of IL-6, and TAEE increased it, not significantly. However, both treatment groups did not increase the serum levels of TNF-α in the hamsters with pigmented gallstones. ^aP < 0.05 between MTBE and TAEE. ^eP < 0.05 vs control (dimethyl sulfoxide). ^aP < 0.05. DMSO: Dimethyl sulfoxide; MTBE: Methyl tert-butyl ether; TAEE: Tert-amyl ethyl ether.