Classifying of hepatotoxicants in primary mouse hepatocytes
Figure 7.1: average values of (A) ALT ; (B) AST, (C) LD and (D) TBIL measured in the cell culture medium of the primary mouse hepatocytes. ** indicates significant values in a student T-test with a P-value ≤ 0.01. * indicates significant values with a P-value ≤ 0.05 compared with the vehicle control, calculated with a student T-test.
RESULTS Clinical parameters In the medium of the primary mouse hepatocytes we measured ALT, AST, LD and TBIL (Figure 7.1). In comparison with the control samples and the other compounds, diclofenac significantly induced ALT, AST and LD. High levels of these metabolic enzymes also indicate an increased amount of cell death despite the application of an IC20 concentration. Surprisingly, tetracycline significantly increased TBIL levels in the medium of the primary mouse hepatocytes. In addition, valproic acid showed a trend for increased TBIL levels in the medium of primary mouse hepatocytes. Increased TBIL levels are usually associated with cholestasis and together with AST it is the most important predictor of drug-induced hepato25 toxicity .
155