Isolated perfused liver
Springer Online Journal Archives 1860-2000
Summary Uptake and hepatotoxicity of 1,1-dichloroethylene (vinylidene chloride, VDC) was investigated with the isolated perfused rat liver: 1. VDC, at concentrations of 670, 2150, 3400, 5000, and 6500 ppm, was evaporated in the thermostat and introduced into the perfusion medium for 3 hours under steady-state conditions. During this period the VDC concentration in the perfusate rose linearly from 4.8 to 34.8μg/ml. 2. The difference between the concentrations in the perfusate, determined before and after hepatic passage (prehepatic and posthepatic concentration, respectively) as a function of the hepatic flux was used to investigate VDC uptake. With increasing prehepatic concentrations of VDC, metabolization approached a saturation characteristic. At a concentration of 4.8μg/ml perfusate, 2.5 pmol/g liver is metabolized within 3 hours, and at 34.8μg/ml the respective value is 8.6μmol/g liver. 3. Inhibitors of microsomal cytochrome P-450-dependent drug metabolism, e.g., 2-diethylaminoethyl-2, 2-diphenylvalerate (SKF 525-A) or 6-nitro-1, 2, 3-benzotthiadiazole (0.02 mmol) decrease the uptake just slightly. Stronger inhibition (40 %) was achieved with pyrazole (200 mmol). 5,6-Dimethyl-1, 2, 3-benzothiadiazole was found inactive. 4. VDC uptake was significantly elevated (35 %) following pretreatment of rats with 1, 1, 1-trichloro-2, 2-bis (p-chlorophenyl)-ethane (DDT) and to a lesser degree after phenobarbital (10 %). This stimulation of the uptake rate was not correlated with enhanced hepatotoxicity of VDC, as evidenced by the concentrations of the serum glutamate-oxaloacetate transaminase (SGOT), the serum glutamate-pyruvate transaminase (SGPT) and they-glutamyl transpeptidase (γ-GT) in the perfusate.
Type of Medium: