title: Furocoumarins affect hepatic cytochrome P450 and renal organic ion transporters in mice.
abstract: Furocoumarins are a group of natural products with many biological activities. Clinical evidences have demonstrated the important contribution of furocoumarins to the toxicity of some foods and herbs. In order to assess liver and kidney toxicity of furocoumarins, male mice were orally administrated with psoralen, isopsoralen, imperatorin, isoimperatorin and xanthotoxin at 20 and 40 mg/kg once daily for 28 days, respectively. No changes of food or water intake were observed in furocoumarins-treated mice. Only 40 mg/kg isopsoralen reduced body weight. 40 mg/kg furocoumarins altered serum activities of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and/or levels of albumin, showing hepatotoxicity. Furthermore, furocoumarins increased activity and protein expression of hepatic microsomal cytochrome P450 (CYP450) 3A11. CYP 2E1 activity and protein expression were suppressed by psoralen and isopsoralen and increased by xanthotoxin. Renal protein levels of organic cation/carnitine transporters (OCT1, OCT2 and OCTN2) and organic anion transporter 3 were increased by most furocoumarins. Renal urate transporter 1, glucose transporter 9 and multidrug resistance protein 4 were influenced by furocoumarins. These findings suggest that furocoumarins may interfere in metabolism, excretion and bioavailability of endogenous and exogenous compounds to impair liver and kidney functions mediated by affecting hepatic CYP450 and renal organic ion transport system.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Lou
authors.forename: Ming-Xing
authors.initials: MX
authors.lastname: Wang
authors.forename: Yun-Wei
authors.initials: YW
authors.lastname: Shi
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Xu
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D027682:Cation Transport Proteins / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D011564:Furocoumarins / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D060888:Real-Time Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D014527:Uric Acid / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D011564:Furocoumarins; D014527:Uric Acid; D003577:Cytochrome P-450 Enzyme System