Pregnane X receptor mediates the induction of P-glycoprotein by spironolactone in HepG2 cells

Highlights ► Spironolactone induces P-gp expression and activity in HepG2 cells. ► The up-regulation of P-gp is likely at transcriptional level. ► This response is mediated by the pregnane X-receptor. ► Up-regulation of P-gp by spironolactone protects cells from doxorubicin toxicity.

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Bibliographic Details
Published in:Toxicology (Amsterdam) 2011-07, Vol.285 (1), p.18-24
Main Authors: Rigalli, Juan Pablo, Ruiz, María Laura, Perdomo, Virginia Gabriela, Villanueva, Silvina Stella Maris, Mottino, Aldo Domingo, Catania, Viviana Alicia
Format: Article
Language:English
Subjects:
ATP-Binding Cassette, Sub-Family B, Member 1 - drug effects
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Biological and medical sciences
biotransformation
Blotting, Western
Cytotoxicity
Dose-Response Relationship, Drug
doxorubicin
Doxorubicin - toxicity
Drug Interactions
Emergency
Hep G2 Cells
HepG2 cells
human cell lines
Humans
ketoconazole
Medical sciences
messenger RNA
Mineralocorticoid Receptor Antagonists - administration & dosage
Mineralocorticoid Receptor Antagonists - pharmacology
P-glycoprotein
Polymerase Chain Reaction
Pregnane X receptor
quantitative polymerase chain reaction
Receptors, Steroid - metabolism
Rhodamine 123 - pharmacokinetics
RNA, Messenger - metabolism
siRNA
small interfering RNA
Spironolactone
Spironolactone - administration & dosage
Spironolactone - pharmacology
Toxicology
transcription (genetics)
Up-Regulation - drug effects
verapamil
Verapamil - pharmacology
viability
Western blotting
xenobiotics
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Description
Summary:Highlights ► Spironolactone induces P-gp expression and activity in HepG2 cells. ► The up-regulation of P-gp is likely at transcriptional level. ► This response is mediated by the pregnane X-receptor. ► Up-regulation of P-gp by spironolactone protects cells from doxorubicin toxicity.
ISSN:0300-483X
1879-3185
DOI:10.1016/j.tox.2011.03.015