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Toxicologic Pathology
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Isolated Hemoperfused Slaughterhouse Livers as a Valid Model to Study Hepatotoxicity

Christian Grosse-Siestrup

Department of Comparative Medicine and Experimental Animal Sciences, Charité School of Medicine, Humboldt-University, Berlin, Germany, christian.grosse-siestrup{at}charite.de

Jeanette Pfeffer

Paul-Ehrlich-Institute, Langen, Germany

Volker Unger

Department of Comparative Medicine and Experimental Animal Sciences, Charité School of Medicine, Humboldt-University, Berlin, Germany

Stefan Nagel

Department of Comparative Medicine and Experimental Animal Sciences, Charité School of Medicine, Humboldt-University, Berlin, Germany

Christian Witt

Department of Medicine, Charité School of Medicine, Humboldt-University, Berlin, Germany

Axel Fischer

Department of Pediatric Pneumology and Immunology, Charité School of Medicine, Humboldt-University, Berlin, Germany

David A. Groneberg

Department of Medicine, Charité School of Medicine, Humboldt-University, Berlin, Germany, david.groneberg{at}charite.de, Department of Pediatric Pneumology and Immunology, Charité School of Medicine, Humboldt-University, Berlin, Germany

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 nonphysiologi c settings, a new model of normothermic hemoperfused isolated porcine slaughterhous e 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.

Key Words: Liver toxicology • hemoperfusion • slaughterhouse • preservation • organ perfusion • diclofenac.

References

Toxicologic Pathology, Vol. 30, No. 6, 749-754 (2002)
DOI: 10.1080/01926230290166841
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Home page
 Toxicol PatholHome page
S. Nagel, O. Hegemann, D. A. Groneberg, and C. Grosse-Siestrup
An Improved Model of Isolated Hemoperfused Porcine Livers Using Pneumatically Driven Pulsating Blood Pumps
Toxicol Pathol, June 1, 2005; 33(4): 434 - 440.
[Abstract] [Full Text] [PDF]

This Article
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