title: Effects of phalloidin on hepatic gene expression in mice.
abstract: An attempt has been made to identify molecular markers of intrahepatic cholestasis in mice employing phalloidin as a cholestatic agent. Phalloidin was administered to BALB/c mice at three predetermined dose: 250 microg/kg, 500 microg/kg, and 1 mg/kg for 1, 3, and 7 days. Liver function was estimated to confirm cholestasis. Histopathological observations on liver were also made to confirm liver injury. Phalloidin at 1 mg/kg for 7 days was found to induce cholestasis. Therefore gene expression studies were confined to this group only. A total of 88 genes were found to be affected by phalloidin. These were the genes associated with cytoskeleton regulation as well as tight junction, focal adhesion, and ATP-binding cassette transporters. Such proteins obstruct the removal of bile components from hepatocytes to the bile canaliculus or blood. Phalloidin treatment did not affect the proteins responsible for cell maintenance or death. The authors show that phalloidin-induced intrahepatic cholestasis is manifested by disturbing the cytoskeleton. The set of genes up-regulated by phalloidin can be considered as molecular markers of intrahepatic cholestasis. The observations are further expected to be helpful in the management of cholestatic pharmaceuticals and associated problems of liver diseases in humans.
authors.affiliation: Toxicogenomics Team, Korea Institute of Toxicology, Yuseong, Daejeon, Republic of Korea.
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Lim
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Hwang
authors.forename: Han-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Yong-Bum
authors.initials: YB
authors.lastname: Kim
authors.forename: Suresh V S
authors.initials: SV
authors.lastname: Rana
authors.forename: Seokjoo
authors.initials: S
authors.lastname: Yoon
mesh_terms: D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010590:Phalloidine / Q000633:toxicity*
chemical_list: D010590:Phalloidine