Digestive Diseases and Sciences

, Volume 40, Issue 2, pp 419–426 | Cite as

Toxic effects of cholelitholytic solvents on gallbladder and liver

A piglet model study
  • Chiung-Yu Chen
  • Kuo-Kuan Chang
  • Nan-Hwa Chow
  • Tay-Chen Leow
  • Tse-Chuan Chou
  • Xi-Zhang Lin
Pancreatic And Biliary Disorders

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 methyltert-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.

Key words

cholelitholysis methyltert-butyl ether ethyl propionate dimethyl sulfoxide tetrasodium ethyldimethyl tetraacetate 

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References

  1. 1.
    Allen MJ, Borody TJ, Bugliosi TF, May GR, LaRusso NF, Thistle JL: Rapid dissolution of gallstones by methyltert-butyl ether: Preliminary observations. N Engl J Med 312:217–220, 1985PubMedGoogle Scholar
  2. 2.
    Thistle JL, May GR, Bender CE, Williams HJ, LeRoy AJ, Nelson PE, Peine CJ, Petersen BT, McCullough JE: Dissolution of cholesterol gallbladder stones by methyltert-butyl ether administered by percutaneous transphepatic catheter. N Engl J Med 320:633–639, 1989PubMedGoogle Scholar
  3. 3.
    Neoptolemos JP, Hall C, O'Connor HJ, Murray WR, Carr-Locke DL: Methyltert-butyl ether for treating bile duct stones: The British experience. Br J Surg 77:32–35, 1990PubMedGoogle Scholar
  4. 4.
    Hofmann AF, Schteingart CD, vanSonnenberg E, Esch O, Zakko SF: Contact dissolution of cholesterol gallstones with organic solvents. Gastroenterol Clin North Am 20:183–199, 1991PubMedGoogle Scholar
  5. 5.
    Zakko SF, Scirica JC, Guttermuth CF, Dodge J, Rashid S, Khan M, Srb SM, Ramsby GR, Hajjar JJ: Ethyl propionate for cholesterol gallstone dissolution: More effective and less cytotoxic than MTBE. Gastroenterology 102:A339, 1992 (abstract)Google Scholar
  6. 6.
    Nakamura Y, Suzuki N, Takahashi W, Sato T: Study on dissolution and disintegration of calcium bilirubinate stone. Tohoku J Exp Med 125:121–134, 1978PubMedGoogle Scholar
  7. 7.
    Leuschner U, Wurbs D, Baumgartel H, Helms EB, Classen M: Alternating treatment of common bile duct stones with a modified glyceryl-1-monooctanoate preparation and a bile acid-EDTA solution by nasobiliary tube. Scand J Gastroenterol 16:497–503, 1981PubMedGoogle Scholar
  8. 8.
    Wosiewitz U, Sabinski F, Haus C, Guldutuna S, Leuschner U: Experimental dissolution of pigment gallstone material using alkaline EDTA and adjuvant bile salts/non-bile salt detergents, thiol and urea, with respect to local chemolysis. J Hepatol 14:7–15, 1992PubMedGoogle Scholar
  9. 9.
    Leuschner U, Baumgartel H, Wosiewitz U: Dissolution of black pigment stones of the gallbladder. Gastroenterology 88:1674, 1985 (abstract)Google Scholar
  10. 10.
    Igimi H, Asakawa S, Kataoka A, Shimura H: Clinical trials of DMSO on the cases with intrahepatic stones. Gastroenterology 88:1666, 1985 (abstract)Google Scholar
  11. 11.
    Dai KY, Montet JC, Zhao XM, Amic J, Montet AM: Dissolution of human brown pigment biliary stones. J Hepatol 9:301–311, 1989PubMedGoogle Scholar
  12. 12.
    Su CH, Lui WY, P'Eng FK: Relative prevalence of gallstone diseases in Taiwan: A nationwide cooperative study. Dig Dis Sci 37:764–768, 1992PubMedGoogle Scholar
  13. 13.
    Nelson PE, Moyer TP, Thistle JL: Dissolution of calcium bilirubinate and calcium carbonate debris remaining after methyl-tert-butyl ether dissolution of cholesterol gallstones. Gastroenterology 98:1345–1350, 1990PubMedGoogle Scholar
  14. 14.
    Esch O, Spinosa JC, Hamilton RL, Crombie DL, Schteingart CD, Rondinone JF, D'Agostino HB, Lillienau J, Hofmann AF: Acute effects of topical methyltert-butyl ether or ethyl propionate on gallbladder histology in animals: A comparison of two solvents for contact dissolution of cholesterol gallstones. Hepatology 16:984–991, 1992PubMedGoogle Scholar
  15. 15.
    vanSonnenberg E, Zakko S, Hofmann AF, D'Agostino HB, Jinich H, Hoyt DB, Miyai K, Ramsby G, Moossa AR: Human gallbladder morphology after gallstone dissolution with methyltert-butyl ether. Gastroenterology 100:1718–1723, 1991PubMedGoogle Scholar
  16. 16.
    Leuschner U, Hellstern A, Schmidt K, Hubner K, Fischer H, Guldutuna S, Jubner K, Leuschner M: Gallstone dissolution with methyltert-butyl ether in 120 patients: Efficacy and safety. Dig Dis Sci 36:193–199, 1991PubMedGoogle Scholar
  17. 17.
    Adam G, Knuechel R, Vorwerk D, Held C, Guenther RW: Tissue response of the biliary and digestive system of rabbits after MTBE infusion into the gallbladder. Invest Radiol 25:58–61, 1990PubMedGoogle Scholar
  18. 18.
    Akimoto R, Rieger E, Moossa AR, Hofmann AF, Wahlstrom HE: Systemic and local toxicity in the rat of methyltert-butyl ether: A gallstone dissolution agent. J Surg Res 53:572–577, 1992PubMedGoogle Scholar
  19. 19.
    Amelsberg A, vanSonnenberg E, Esch O, Schteingart CD, Hofmann AF: Contact dissolution of cholesterol gallstones with ethyl propionate (EP): Further clinical experience. Hepatology 18:98A, 1993 (abstract)Google Scholar
  20. 20.
    Esch O, Schteingart CD, Pappert D, Kirby D, Streich R, Hofmann AF: Increased blood levels of methyl tert-butyl ether but not of ethyl propionate during instillation with contact gallstone dissolution agents in the pig. Hepatology 18:373–379, 1993PubMedGoogle Scholar
  21. 21.
    Lohse J, Verine HJ, Sarles H: Study on pancreatic stones. Digestion 21:125–132, 1981PubMedGoogle Scholar
  22. 22.
    Dretler SP, Pfister RC, Newhouse JH: Renal-stone dissolution via percutaneous nephrostomy. N Engl J Med 300:341–343, 1979PubMedGoogle Scholar
  23. 23.
    Lin XZ, Lin CY, Chang TT, Shin JS, Liou TC, Chang KK: Choloedocholithiasis treated by ethylenediamine tetraacetic acid infusion through endoscopic nasobiliary catheter. J Gastroenterol Hepatol 7:335–338, 1992PubMedGoogle Scholar
  24. 24.
    Duffy MA, Williams C, Hiller KV, Schumacher MM, Karst EA, Akerlind JK, Napolitano LV: Physicians' Desk Reference, 47 ed. Montvale, New Jersey, Medical Economics Data, 1993, p 1907Google Scholar
  25. 25.
    Cohen AS: Amyloidosis.In Harrison's Principles of Internal Medicine, 12th ed. JD Wilson, E Braunwald, KJ Isselbacher, RG Petersdorf, JB Martin, AS Fauci, RK Root (eds). New York, McGraw-Hill, 1991, pp 1417–1421Google Scholar
  26. 26.
    Muther RS, Bennett WM: Effects of dimethyl sulfoxide on renal function in man. JAMA 244:2081–2083, 1980PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Chiung-Yu Chen
    • 3
    • 1
    • 2
  • Kuo-Kuan Chang
    • 3
    • 1
    • 2
  • Nan-Hwa Chow
    • 3
    • 1
    • 2
  • Tay-Chen Leow
    • 3
    • 1
    • 2
  • Tse-Chuan Chou
    • 3
    • 1
    • 2
  • Xi-Zhang Lin
    • 3
    • 1
    • 2
  1. 1.Department of PathologyNational Cheng Kung UniversityTainanTaiwan
  2. 2.Department of Chemical EngineeringNational Cheng Kung UnivesityTainanTaiwan
  3. 3.Division of Gastroenterology, Department of Internal MedicineNational Cheng Kung University HospitalTainanTaiwan

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