Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model.
Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.
Porquet
D
D
U.F.R. des Sciences Pharmaceutiques et Biologiques, Département de Biochimie, Châtenay-Malabry, France.
Appel
M
M
Fournier
T
T
Bertaux
O
O
Biou
D
D
Féger
J
J
D000818:Animals; D001769:Blood; D015152:Blotting, Northern; D005069:Evaluation Studies as Topic; D008099:Liver / Q000187:drug effects*; D008297:Male; D009961:Orosomucoid / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D014116:Toxicology / Q000379:methods*; D014749:Vincamine / Q000031:analogs & derivatives* / Q000633:toxicity*
D009961:Orosomucoid; D012313:RNA; D014749:Vincamine; C044616:vindeburnol