Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats.
Estimation of liver damage is important in the pathophysiological and toxicological study of liver disease. As a novel, non-invasive marker of liver damage, we studied the efficacy of urine bile acids (UBA) in a rat model of liver disease. Thioacetamide (TAA)-treated rats were used in this study. Single intraperitoneal administration of high-dose TAA induces severe damage to the liver, and thus is used as a model of acute hepatitis. Continuous administration of low-dose TAA yields mild damage to the liver, and induces cirrhosis and hepatic tumors. In this study, it was found that both acute and chronic administration of TAA was associated with a dose-dependent elevation of UBA. The elevation of UBA content correlated with the alteration of blood biochemical indicators, and UBA screening showed a remarkable ability to distinguish liver-damaged rats from healthy rats. In particular, UBA analysis was found to have high sensitivity, specificity, and positive predictive value for the screening of rats with abnormal serum alkaline phosphatase (ALP) activity due to chronic liver damage, which was confirmed to include cholestasis and subsequent cirrhosis by liver histological analysis. In conclusion, we demonstrated that measurement of UBA is a simple, non-invasive and effective method for the screening of cholestasis in TAA-treated rats. We suggest that UBA analysis may have potent applicability for monitoring the progress of liver damage in animal models of chronic liver disease, such as cirrhosis and hepatic encephalopathy.
Kawai
Hiroshi
H
Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8555, Japan. hkawai@jiu.ac.jp
Kudo
Naomi
N
Kawashima
Yoichi
Y
Mitsumoto
Atsushi
A
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001647:Bile Acids and Salts / Q000652:urine*; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007274:Injections, Intraperitoneal; D008107:Liver Diseases / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000097:blood / Q000633:toxicity
D001647:Bile Acids and Salts; D013853:Thioacetamide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase