Use of Ursodeoxycholic Acids in a Dog With Chronic Hepatitis: Effects on Serum Hepatic Tests and Endogenous Bile Acid Composition
Denny J. Meyer
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL
CVD-IDEXX, Inc, 285 KOVR Dr, W. Sacramento, CA 95605–1600.
Search for more papers by this authorMorrow B. Thompson
National Institute of Environmental Health Sciences, Research Triangle Park, NC
Search for more papers by this authorDavid F. Senior
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana Stale University, Baton Rouge, LA
Search for more papers by this authorDenny J. Meyer
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL
CVD-IDEXX, Inc, 285 KOVR Dr, W. Sacramento, CA 95605–1600.
Search for more papers by this authorMorrow B. Thompson
National Institute of Environmental Health Sciences, Research Triangle Park, NC
Search for more papers by this authorDavid F. Senior
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana Stale University, Baton Rouge, LA
Search for more papers by this authorAbstract
A dog with severe cholestasis secondary to chronic hepatitis was treated with ursodeoxycholic acid (UDCA1 PO. After 2 weeks of daily treatment, the dog was more active and had an improved appetite. Monthly serum biochemical determinations and analysis of individual bile acid profiles documented improvement in hepatobiliary tests and a marked reduction in the concentrations of potentially hepatotoxic endogenous bile acids. These effects were maintained for approximately 6 months- The findings in this dog are similar to those reported for human patients treated with UDCA and provide preliminary evidence in support of its continued evaluation in the treatment of cholestatic liver disease in the dog.
References
- 1 Schmucker DL, Ohta M., Kanai S., et al. Hepatic injury induced by bile salts: Correlation between biochemical and morphological events. J Hepatol 1990; 12: 1216–1221.
- 2 Angelico M., Del Vecchio C., Nistri A. Effect of tauroursodeoxycholic acid on serum liver enzyme and serum lipid levels in patients with chronic active hepatitis. Curr Ther Res 1995; 56: 626–634.
- 3 Combes B., Carithers RL Jr, Maddrey WC, et al. A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1995; 22: 759–766.
- 4 Marteau P., Chazouillieres O., Myara A., et al. Effect of chronic administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acids in man. Hepatology 1990; 12: 1206–1208.
- 5 Thompson MB, Blair PC, Morris RW, et al. Validation and application of a liquid-chromatographic/enzymatic assay for individual bile acids in the serum of rats. Clin Chem 1987; 33: 1856–1862.
- 6 Thompson MB, Chappell JD, Kunze DJ, et al. Bile acid profile in a dog with cholangiocarcinoma. Vet Pathol 1989; 26: 75–78.
- 7 Hillaire S., Ballet F., Franco D., et al. Effects of ursodeoxycholic acid and chenodeoxycholic acid on human hepatocytes in primary culture. Hepatology 1995; 22: 82–87.
- 8 Hofmann AF. Bile acid secretion, bile flow and biliary lipid secretion in humans. Hepatology 1990; 12: 17S–25S.
- 9 Sokol RJ, Winklhofer-Roob BM, Devereaux MW, et al. Generation of hydroperoxides in isolated rat hepatocytes and hepatic mitochondria exposed to hydrophobic bile acids. Gastroenterology 1995; 109: 1249–1256.
- 10 Bertolotti M., Abate N., Loria P., et al. Regulation of bile acid synthesis in humans: Effect of treatment with bile acids, cholestyramine or simvastatin on cholesterol 7α-hydroxylase rates in vivo. Hepatology 1991; 14: 830–837.
- 11 Poupon RE, Ouguerram K., Chretien Y., et al. Cholesterol-lowering effect of ursodeoxycholic acid in patients with primary biliary cirrhosis. Hepatology 1993; 17: 577–582.
- 12 Vlahcevic ZR, Heuman DM, Hylemon PB. Regulation of bile acid synthesis. Hepatology 1991; 13: 590–600.
- 13 Rudolph G., Endle R., Senn M., et al. Effect of ursodeoxycholic acid on the kinetics of cholic acid and chenodeoxycholic acid in patients with primary sclerosing cholangitis. Hepatology 1993; 17: 1028–1032.
- 14
Hoffman AF.
Pharmacology of ursodeoxycholic acid, an enterohepatic drug.
Scand J Gastroenterol
1994; 29: S1–S15.
10.3109/00365529409103618 Google Scholar
- 15 Einarsson K. Effect of ursodeoxycholic acid on hepatic cholesterol metabolism. Scand J Gastroenterol 1994; 204: 19–23.
- 16 Stiehl A., Raedsch R., Rudolph G. Acute effects of ursodeoxycholic and chenodeoxycholic acid on the small intestinal absorption of bile acids. Gastroenterology 1990; 98: 424–428.
- 17 Friman S., Thune A., Nilsson B., et al. Medication with ursodeoxycholic acid enhances the biliary clearance of polyethylene glycol 900 but not mannitol. Digestion 1995; 56: 382–388.
- 18 Shimokura GH, McGill JM, Schlenker T., et al. Ursodeoxycholate increases cytosolic calcium concentration and activates Cl-currents in a biliary cell line. Gastroenterology 1995; 109: 965–972.
- 19 Anwer MS. Mechanism of bile acid-induced HCO--rich hypercholeresis: An analysis based on quantitated acid-base chemistry. J Hepatol 1992; 14: 118–126.
- 20 Neuman MG, Cameron RG, Shear NH, et al. Effect of tauroursodeoxycholic and ursodeoxycholic acid on ethanol-induced cell injuries in human Hep G2 cell line. Gastroenterology 1995; 109: 555–563.
- 21 Krahenbuhl S., Fischer S., Talos C., et al. Ursodeoxycholate protects oxidative mitochondrial metabolism from bile acid toxicity: Dose-response study in isolated rat liver mitochondria. Hepatology 1994; 20: 1595–1601.
- 22 Scholmerich J., Baumgartner U., Miyai K., et al. Tauroursodeoxycholate prevents taurolithocholate-induced cholestasis and toxicity in rat liver. J Hepatol 1990; 10: 280–283.
- 23 Heuman DM, Mills A., McCall J., et al. Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. Gastroenterology 1991; 100: 203–211.
- 24 Kurktschiev D., Subat S., Adler D., et al. Immunomodulating effect of ursodeoxycholic acid therapy in patients with primary biliary cirrhosis. J Hepatol 1993; 18: 373–377.
- 25 Yoshikawa M., Tsujii T., Matsumura K., et al. Immunomodulatory effects of ursodeoxycholic acid on immune responses. Hepatology 1992; 16: 358–364.
Citing Literature
