Isolated hemoperfused slaughterhouse livers as a valid model to study hepatotoxicity.
Different models of isolated and perfused livers and precision cut liver slices have been developed for studies on liver toxicology the past years. As most of these models were limited by nonphysiologic settings, a new model of normothermic hemoperfused isolated porcine slaughterhouse livers to examine hepatotoxicity was established encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. As model compound, the analgesic substance diclofenac was used and the effects of this drug on organ function parameters were compared to an untreated control group. Using an amount of 2,000 ml, the organs were perfused over 180 minutes, metabolically controlled via a dialysis and oxygenation system and various hematological and hepatic parameters were examined. In contrast to the untreated control organs, significant differences were found in the diclofenac group for parameters such as lactate, creatinine, ALT, bicarbonate, or bile flow. In summary, the presently established model of isolated hemoperfused slaughterhouse livers displays a useful new approach to assess hepatotoxicity of different substances on the organ level. As a major economic advantage in comparison to setups using laboratory animals, the new model can be run with blood and organs obtained from slaughterhouse animals.
Grosse-Siestrup
Christian
C
Department of Comparative Medicine and Experimental Animal Sciences, Charité School of Medicine, Humboldt-University, Berlin, Germany. christian.grosse-siestrup@charite.de
Pfeffer
Jeanette
J
Unger
Volker
V
Nagel
Stefan
S
Witt
Christian
C
Fischer
Axel
A
Groneberg
David A
DA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001804:Blood Transfusion, Autologous; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004008:Diclofenac / Q000633:toxicity*; D004195:Disease Models, Animal; D006464:Hemoperfusion / Q000379:methods*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009926:Organ Preservation / Q000379:methods; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac