Members of the vitamin E family or their metabolites may induce the xenobiotic transporter P‐glycoprotein (P‐gp), which can limit the bioavailability of drugs and phytochemicals. This study aimed to investigate if α‐ and γ‐tocopherol, α‐ and γ‐tocotrienol, the long chain metabolite α‐tocopherol‐13’‐COOH, the short chain metabolites α‐ and γ‐carboxyethylhydroxychromanol and plastochromanol‐8 activate the pregnane X receptor (PXR) and thereby modulate P‐gp expression and/or activity.
Methods and results
P‐gp protein expression and activity were studied in LS 180 cells incubated with the respective test compound for 48 h. Furthermore, we determined if the compounds activate PXR in LS 180 cells, as PXR regulates P‐gp expression. Neither P‐gp protein expression and activity, nor PXR activity were influenced by α‐tocopherol, γ‐tocopherol and plastochromanol‐8. α‐Tocotrienol activated PXR in the reporter gene assay but did not induce protein expression or activity of P‐gp. γ‐Tocotrienol and α‐13’‐COOH activated PXR and induced protein expression and transporter activity of P‐gp.
Because the induction of P‐gp in the intestine may limit the systemic bioavailability of its substrates, the concurrent intake of drugs and γ‐tocotrienol and, if ever applicable, α‐13’‐COOH should be avoided.
Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.