Hepatotoxic effects of polidocanol in a model of autologously perfused porcine livers.
Polidocanol is an effective sclerosing agent that consists of 95% hydroxypolyethoxydodecane and 5% ethyl alcohol and is known to have a low risk of complications. However, since the compound has been proposed for the local treatment of liver diseases, the potential for topical hepatic side effects should be examined. Therefore, the new model of normothermic-hemoperfused isolated porcine slaughterhouse livers was used to examine polidocanol-hepatotoxicity encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. Polidocanol was administered via the hepatic artery and portal vein and the effects of the sclerosant on organ function parameters were compared with those in an untreated control group. In contrast to the untreated control organs, significant differences were found in the polidocanol group for parameters such as alanine aminotransferase or organ weight after perfusion. The most striking differences were found for hepatic bile flow, which dropped in the polidocanol group to 0.24+/-0.02 ml/min per 1000 g after administration of the compound compared with 3.80+/-1.08 ml/min per 1000 g in the control group. In summary, the present observations indicate a risk of hepatotoxic effects of polidocanol. Clinicians should be aware of this problem and the use of polidocanol for intrahepatic sclerosing should be restricted to specialized centers.
Grosse-Siestrup
Christian
C
Department of Comparative Medicine and Experimental Animal Sciences, Charité School of Medicine, Free University and Humboldt-University, 13353 Berlin, Germany.
Unger
Volker
V
Pfeffer
Jeanette
J
Dinh
Q Thai
QT
Nagel
Stefan
S
Springer
Jochen
J
Witt
Christian
C
Wussow
Anke
A
Groneberg
David A
DA
D000826:Animal Testing Alternatives; D000818:Animals; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D010477:Perfusion; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000633:toxicity*; D012597:Sclerosing Solutions / Q000633:toxicity*; D013552:Swine; D018675:Toxicity Tests / Q000379:methods*
D012597:Sclerosing Solutions; D000077423:Polidocanol; D011092:Polyethylene Glycols