Litholysis Effect and Biological Safety of Different Ethers for Gallbladder Stones / 胃肠病学

ABSTRACT

Background:Dissolution therapy is used as an alternative to surgery in patients with gallbladder stone and contraindication for surgery.Finding medicines with optimal litholysis effect and low cytotoxicity is of great importance in clinical practice.Aims:To study the litholysis effect and biological safety of different ethers for gallbladder stones.Methods:Methyl tertiary-butyl ether (MTBE),ethyl tertiary-butyl ether (ETBE),ethylene glycol mono-tert-butyl ether (ETB),and di (ethylene glycol) tert-butyl ether (DETB),arranged by the order of relative molecular weight,were used to dissolve the gallbladder stones in vitro.Normal human liver cell line LO2 was treated with the above mentioned four ethers,and the cell viability was assessed by CCK-8 assay for analyzing the proliferative toxicity.Thirty Sprague-Dawley rats were administered intragastrically with the four ethers for 2 weeks,and then the serum biochemical indices and histopathology of liver,lung,kidney,stomach,duodenum and jejunum were examined.Results:The litholysis effect of MTBE was the most prominent (P ＜ 0.05);that of ETB and DETB were weaker than ETBE (P ＜ 0.05) but still had a substantial effect.CCK-8 assay showed that ETBE was the most toxic ether (P ＜ 0.05),and the proliferative toxicity of ETB and DETB was similar (P ＞ 0.05).Except for the slightly increased serum AST in MTBE,ETBE and ETB groups (P ＜ 0.05),the four ethers had no significant impact on serum biochemical indices and histopathology of multiple organs of the model rats.Conclusions:The increase of relative molecular weight of ether may reduce its litholysis effect,but meanwhile its biological safety is increased.