The hepatotoxicity of chloroform in precision-cut rat liver slices.
Chloroform hepatotoxicity was investigated in precision-cut liver slices from male Sprague-Dawley rats pretreated with phenobarbital to predispose animals to CHCl3 intoxication. Liver slices were exposed to 0.2, 0.5 and 1.0 mM chloroform for a total of 9 h in a roller culture system. Intracellular K+ loss was found to be concentration- and time-dependent over the duration of the experiment. Histopathological changes were also evident. Glucose 6-phosphate dehydrogenase and beta-glucuronidase were significantly decreased at 3 h relative to controls where a loss of 61% and 36% occurred, respectively. Enzyme levels of alanine aminotransferase and lactate dehydrogenase, both found predominantly in periportal hepatocytes, remained identical to controls over the duration of the experiment. A significant time-dependent depletion of glutathione occurred as early as 3 h following the administration of 0.5 mM chloroform. Mitochondrial viability, measured by the reduction of a specific dye, was significantly lower than controls in treated slices at 6 h following chloroform administration. Precision-cut liver slices appear to be especially useful for the biochemical and histopathological examination of site-specific hepatotoxicants such as CHCl3.
Azri-Meehan
S
S
Department of Anesthesiology, College of Medicine, University of Arizona, Tucson 85724.
Mata
H P
HP
Gandolfi
A J
AJ
Brendel
K
K
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002725:Chloroform / Q000633:toxicity*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002725:Chloroform; D005954:Glucosephosphate Dehydrogenase; D005966:Glucuronidase; D011188:Potassium