The long chain α–tocopherol metabolite α‐13’‐COOH and γ‐tocotrienol induce P‐glycoprotein expression and activity by activation of the pregnane X receptor in the intestinal cell line LS 180

Abstract

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.

Structure–Function Relationship Studies In Vitro Reveal Distinct and Specific Effects of Long‐Chain Metabolites of Vitamin E

“…Further catabolism of the LCM shortens the side chain, leading to intermediate‐chain metabolites (ICM) and finally to water soluble short‐chain metabolites (SCM; carboxyethylhydroxychromanols, CEHC) . At present, knowledge about the physiological function and importance of the LCM is limited …”

The Hepatic Fate of Vitamin E

“…Interestingly, α-, δ-, and γ-TOH as well as α-and γ-T3 activated PXR in HepG2 liver cells transfected with human PXR and chloramphenicol acetyl transferase linked to two PXR responsive elements [81], while α-and γ-TOH as well as their metabolites α-and γ-CEHC did not in transfected colon carcinoma cells [82]. However, the LCM α-13′-COOH activated PXR in the latter cellular system and so did γ-T3 [82]. This finding implicates that the LCM of TOH are the responsible mediators of reported TOH actions via PXR.…”

“…Hence, vitamin E might regulate its metabolism by binding to PXR and subsequent alteration of the expression of the enzymes involved in the first catabolic step. Indeed, studies using cells transfected with reporter genes provided evidence for an activation of PXR by different vitamin E structures (i.e., TOHs, T3s, and metabolites) [81,82]. Interestingly, α-, δ-, and γ-TOH as well as α-and γ-T3 activated PXR in HepG2 liver cells transfected with human PXR and chloramphenicol acetyl transferase linked to two PXR responsive elements [81], while α-and γ-TOH as well as their metabolites α-and γ-CEHC did not in transfected colon carcinoma cells [82].…”

Vitamin E intestinal absorption: Regulation of membrane transport across the enterocyte

“…This downregulation may be due to a reduction of lipid peroxidation and cellular oxidative stress or to an inhibition of tyrosine kinase . Although not demonstrated, such regulation by vitamin E may also involve transcription factors such as PXR (pregnane X receptor) , possibly via its long chain metabolite α‐tocopherol‐13’‐COOH .…”