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溶石溶剂对胆囊和肝脏的毒性作用。一项仔猪模型研究。

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

作者信息

Chen C Y, Chang K K, Chow N H, Leow T C, Chou T C, Lin X Z

机构信息

Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Dig Dis Sci. 1995 Feb;40(2):419-26. doi: 10.1007/BF02065431.

DOI:10.1007/BF02065431
PMID:7851209
Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

我们在动物模型中评估了四种目前使用的化学溶解溶剂——二甲基亚砜(DMSO,99%)、丙酸乙酯(EP,99%)、乙二甲基四乙酸四钠(4Na - EDTA,2%,pH 11)和甲基叔丁基醚(MTBE,纯度 = 99.5%)的毒性作用。每种溶剂在9头体重20至25千克的长白仔猪身上进行测试。在每次实验前24小时,使用超声引导经肝将一根耐溶剂导管插入胆囊(GB)。每种溶剂75毫升在3小时内注入胆囊。第二天,进行剖腹手术以评估肝脏、胆囊、胆管(BD)或肠道是否可能受损。切除胆囊和肝脏并检查其组织学。为描述组织损伤,对胆囊、胆管和肝脏标本指定以下病理分级:正常(0)、轻度(1)、中度(2)和重度(3)。我们发现,DMSO在胆囊和胆管损伤方面得分最高(49,3),其次是EP(36,2)、EDTA(14,1)和MTBE(16,0);胆囊损伤差异具有统计学意义。DMSO组(2)和MTBE组(2)存在非常轻微的肝细胞损伤。EP和EDTA的给药未导致任何肝脏损伤。每个治疗组内的仔猪都有不同程度的组织损伤。没有死亡归因于所施用的溶剂。我们得出结论,DMSO、EP、EDTA和MTBE对胆囊、胆管和肠道没有严重的局部毒性作用;它们也不会导致严重的肝毒性。(摘要截断于250字)

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引用本文的文献

1
Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate.使用丙酸乙酯成功实现胆固醇性胆囊结石的局部溶解。
Dig Dis Sci. 1997 Jun;42(6):1274-82. doi: 10.1023/a:1018818527187.
2
Local and systemic effects of intraduodenal exposure to topical gallstone solvents ethyl propionate and methyl tert-butyl ether in the rabbit.兔十二指肠内接触局部用胆结石溶剂丙酸乙酯和甲基叔丁基醚的局部和全身效应
Dig Dis Sci. 1997 Mar;42(3):497-502. doi: 10.1023/a:1018830622508.

本文引用的文献

1
Increased blood levels of methyl tert-butyl ether but not of ethyl propionate during instillation with contact gallstone dissolution agents in the pig.在给猪滴注接触性胆结石溶解剂期间,甲基叔丁基醚的血液水平升高,但丙酸乙酯的血液水平未升高。
Hepatology. 1993 Aug;18(2):373-9.
2
Studies on pancreatic stones. I. In vitro dissolution.胰腺结石研究。I. 体外溶解。
Digestion. 1981;21(3):125-32. doi: 10.1159/000198553.
3
Effects of dimethyl sulfoxide on renal function in man.二甲基亚砜对人体肾功能的影响。
JAMA. 1980 Nov 7;244(18):2081-3.
4
Alternating treatment of common bile duct stones with a modified glyceryl-1-monooctanoate preparation and a bile acid-EDTA solution by nasobiliary tube.经鼻胆管交替使用改良单辛酸甘油酯制剂和胆汁酸 - 乙二胺四乙酸溶液治疗胆总管结石
Scand J Gastroenterol. 1981;16(4):497-503. doi: 10.3109/00365528109182004.
5
Rapid dissolution of gallstones by methyl tert-butyl ether. Preliminary observations.甲基叔丁基醚对胆结石的快速溶解作用。初步观察结果
N Engl J Med. 1985 Jan 24;312(4):217-20. doi: 10.1056/NEJM198501243120406.
6
Dissolution of cholesterol gallbladder stones by methyl tert-butyl ether administered by percutaneous transhepatic catheter.经皮经肝胆管导管注入甲基叔丁基醚溶解胆固醇性胆囊结石
N Engl J Med. 1989 Mar 9;320(10):633-9. doi: 10.1056/NEJM198903093201004.
7
Dissolution of human brown pigment biliary stones.人棕色色素胆结石的溶解
J Hepatol. 1989 Nov;9(3):301-11. doi: 10.1016/0168-8278(89)90138-4.
8
Dissolution of calcium bilirubinate and calcium carbonate debris remaining after methyl tert-butyl ether dissolution of cholesterol gallstones.胆固醇性胆结石经甲基叔丁基醚溶解后残留的胆红素钙和碳酸钙碎片的溶解。
Gastroenterology. 1990 May;98(5 Pt 1):1345-50. doi: 10.1016/0016-5085(90)90355-5.
9
Methyl-tert-butyl-ether for treating bile duct stones: the British experience.
Br J Surg. 1990 Jan;77(1):32-5. doi: 10.1002/bjs.1800770111.
10
Tissue response of the biliary and digestive system of rabbits after MTBE infusion into the gallbladder.
Invest Radiol. 1990 Jan;25(1):58-61. doi: 10.1097/00004424-199001000-00015.