The use of isolated rat hepatocyte in prescreening of hepatotoxicants: observation on toxic effects of 14 compounds.
Fourteen compounds, differing in structure, mechanism of action, and primary target organs, were tested for cytotoxic responses in isolated hepatocyte suspensions prepared by a nonperfusion method from male Sprague-Dawley rats. The trypan blue exclusion test, measurement of enzyme activities in supernatants, and enzyme histochemistry were taken as indexes of cytotoxicity. All 14 compounds inhibited enzyme activities in hepatocytes. However, the activities of GOT and LDH in supernatants increased after exposure to the three haloalkanes, but decreased after exposure to the other chemicals (Na2CrO4, etc.). The number of dyed cells increased after exposure to six haloalkanes and the order of their relative toxicities in vitro was roughly in concordance with that of their in vivo hepatoxicities. These results indicate that isolated hepatocytes are useful for prescreening of potential hepatotoxicants; the so-called "enzyme leakage" should be replaced by "enzyme in supernatant" to reflect toxicities of different kinds of compounds; enzyme histochemistry is also a sensitive index in toxicological tests with isolated rat hepatocytes.
Liu
Y F
YF
School of Public Health, West China University of Medical Sciences, Chengdu Sichuan.
Xiao
B L
BL
Liu
Y Q
YQ
Li
S Q
SQ
Zhan
C L
CL
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014343:Trypan Blue
D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D014343:Trypan Blue