Autor:innen:
R. Dolscheid-Pommerich (Bonn, DE)
F. Schneider (Bonn, DE)
M. Hebest (Bonn, DE)
L. Teichmann (Bonn, DE)
R. Koerber (Bonn, DE)
M. Praktiknjo (Bonn, DE)
B. Stoffel-Wagner (Bonn, DE)
J. Chang (Bonn, DE)
Introduction
Cirrhosis is the common end-stage of liver disease. Established animal models of experimental cirrhosis have been widely used to study human pathogenesis of chronic liver disease and portal hypertension. Two of the most successful and reproducible models are a cholestatic model of bile-duct ligation (BDL) and a toxic model induced by exposure to carbon tetrachloride (CCL4). In the context of these models, some of the liver-related laboratory parameters have been investigated in the past. However, there are no standard laboratory parameter ranges for these models.
Material and Methods
To induce cholestatic cirrhosis (BDL), in male Sprague-Dawley rats (Charles River, Sulzfeld, Germany) the bile duct was exposed after median laparotomy, ligated twice and dissected between the two ligatures. For toxic cirrhosis, the animals were exposed to CCL4 inhalation twice weekly in increasing intervals. Blood samples from these models and from healthy control animals were taken at defined timepoints. Analyses were carried out at the central laboratory. Sodium and potassium were determined potentiometrically (cobas 8000 ISE, Roche Diagnostics). Total protein, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, triglycerides, cholesterol, high and low density-lipoprotein cholesterol, direct and total bilirubin, creatinine, and urea nitrogen were determined with cobas c702 or c502 (Roche Diagnostics). Mean, median, standard deviation, minimum and maximum, 2.5-97.5, 5-95 or 10-90 percentiles (depending on group size) were calculated.
Results:
AST, ALT were slightly elevated in healthy controls compared to human reference ranges. Different stages of cirrhosis in BDL and CCL4 models showed distinct differences in liver-related parameters. In BDL rats, the development of clinical and laboratory features, such as weight changes, hypalbuminemia and hyperbilirubinemia, was similar to that of human cirrhosis. Kidney function worsened with progression of cirrhosis. In CCL4 rats, bilirubin was only slightly elevated, even in more advanced stages, compared to healthy controls. Over time, liver-related parameters worsened. In general, changes in laboratory parameters were more pronounced in the BDL model than in the CCL4 model. Interestingly, sodium levels did not differ between control animals and models of cirrhosis nor between compensated and more decompensated stages of cirrhosis.
Conclusion
Standardizing laboratory values in experimental cirrhosis in rodents is of utmost importance. However, existing data mostly focus on few parameters in treated groups. With our data, we provide a much needed overview of standard laboratory values in experimental cirrhosis models and healthy controls in male Sprague Dawley rats. Our data show that some laboratory features behave in a similar manner to human cirrhosis (albumin, liver parameters), while others, such as sodium, do not.