Journal article

Publication year: 2007

Pages: 2070-2077

Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes

Volume number: 1768

Issue number: 9

ISSN: 0005-2736

eISSN: 1879-2642

Open access status: Bronze

DOI Link: https://doi.org/10.1016/j.bbamem.2007.07.006

Publisher: Elsevier

Abstract: 
To determine which efflux carriers are involved in hepatic phalloidin elimination, hepatobiliary [H-3]-demethylphalloin (DMP) excretion was studied in normal Wistar rats and in Mrp2 deficient TR(-) Wistar rats as well as in normal wild-type FVB mice, Mdr1 a,b(-/-) knockout mice, and Bcrp 1(-/-) knockout mice by in situ bile duct/gallbladder cannulation. A subtoxic dose of 0.03 mg DMP/kg b.w. was used, which did not induce cholestasis in any tested animal. Excretion of DMP into bile was not altered in Mdr1a,b(-/-) mice or in Bcrp I(-/-) mice compared with wild-type FVB mice. Whereas 17.6% of the applied dose was excreted into bile of normal Wistar rats, hepatobiliary excretion decreased to 7.9% in TR(-) rats within 2 h after intravenous application. This decrease was not due to reduced cellular DMP uptake, as shown by normal expression of Oatplb2 in livers of TR(-) rats and functional DNIP uptake into isolated TR(-) rat hepatocytes. Tissue concentrations of phalloidin were also not altered in any of the transgenic mice. Interestingly, the decrease of biliary DMP excretion in the TR(-) rats was not followed by any increase of phalloidin accumulation in the liver but yielded a compensatory excretion of the toxin into urine, indicating that hepatocytes of TR(-) rats expelled phalloidin back into blood circulation. (C) 2007 Elsevier B.V. All rights reserved.

Harvard Citation style: Gavrilova, O., Geyer, J. and Petzinger, E. (2007) In vivo relevance of Mrp2-mediated biliary excretion of the Amanita mushroom toxin demethylphalloin, Biochimica et Biophysica Acta (BBA) - Biomembranes, 1768(9), pp. 2070-2077. https://doi.org/10.1016/j.bbamem.2007.07.006

APA Citation style: Gavrilova, O., Geyer, J., & Petzinger, E. (2007). In vivo relevance of Mrp2-mediated biliary excretion of the Amanita mushroom toxin demethylphalloin. Biochimica et Biophysica Acta (BBA) - Biomembranes. 1768(9), 2070-2077. https://doi.org/10.1016/j.bbamem.2007.07.006