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.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Wang X,Lou YJ,Wang MX,Shi YW,Xu HX,Kong LD

doi

10.1016/j.toxlet.2011.11.030

subject

Has Abstract

pub_date

2012-02-25 00:00:00

pages

67-77

issue

1

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(11)01649-3

journal_volume

209

pub_type

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