Herbal hepatotoxicity Felix Stickel, Eleonora Patsenker, Detlef Schuppan  Journal of Hepatology  Volume 43, Issue 5, Pages 901-910 (November 2005) DOI: 10.1016/j.jhep.2005.08.002 Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Histological section (hematoxylin-eosin stained) showing acute veno-occlusive disease in a 18-month-old boy following the ingestion of Tussilago farfara which contains the pyrrolizidine alkaloid seneciophylline. Of note are nonthrombotic occlusion of the central vein and massive hepatic congestion (arrows) which are associated with perivenular necrosis (arrowheads). Neither fibrosis nor inflammation are evident (Courtesy O. Dietze, Salzburg, Austria). Journal of Hepatology 2005 43, 901-910DOI: (10.1016/j.jhep.2005.08.002) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Enzymatic transformation of pyrrolizidine alkaloids into non-toxic alkaloid N-oxides. Comedication with microsomal enzyme inducers (e.g. phenobarbital) favors the formation of toxic pyrroles by several microsomal cytochrome P450 enzymes including CYP 3A4, 2B6, and 2C. Journal of Hepatology 2005 43, 901-910DOI: (10.1016/j.jhep.2005.08.002) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 3 Cytochrome P450 3A activates furane neo-clerodane diterpenoids contained in germander into toxic epoxides. The latter may be neutralized by conjugation with glutathione. In conditions of glutathione deficiency (as in starvation), epoxides may react with hepatic proteins and lead to liver cell death through the induction of apoptosis [48,49]. Journal of Hepatology 2005 43, 901-910DOI: (10.1016/j.jhep.2005.08.002) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions