Use of hepatocyte co-cultures in the assessment of drug toxicity from chronic exposure.
1. In rat hepatocyte cultures, clonidine and malotilate were cytotoxic at 170 microM but did not induce changes at lower concentrations during 24 h exposure. Amitriptyline induced cell injury at 20 microM but was ineffective at 2 microM. 2. In co-culture of rat or human hepatocytes with rat liver epithelial cells, 2 microM amitriptyline was cytotoxic after 7 days treatment whereas 70 to 100 microM clonidine or malotilate gave no significant effect. 3. These results suggest that co-cultured hepatocytes which retain their differentiated state for several days or weeks, represents a promising tool for studying hepatotoxicity from chronic treatment in vitro.
Unité de Recherches Hépatologiques, U 49 INSERM, Hôpital de Pontchaillou, Rennes, France.
D
D
Ratanasavanh
G
G
Baffet
M F
MF
Latinier
M
M
Rissel
A
A
Guillouzo
D000639:Amitriptyline / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003000:Clonidine / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008314:Malonates / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D008314:Malonates; D000639:Amitriptyline; D007770:L-Lactate Dehydrogenase; D003000:Clonidine; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate