Modulation of Cyp3a11 mRNA expression by α-tocopherol but not γ-tocotrienol in mice

Kluth, Dirk; Landes, Nico; Pfluger, Paul T.; Müller-Schmehl, Katrin; Weiss, Kathrin; Bumke-Vogt, Christiane; Ristow, Michael; Brigelius‐Flohé, Regina

doi:10.1016/j.freeradbiomed.2004.11.010

Cited by 65 publications

(52 citation statements)

References 52 publications

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“…Further evidence is given by the α-TOHdependent regulation of CYP3A4 [165] . Feeding mice with 200 mg/d of α-TOH for nine months resulted in 1.7-fold higher Cyp3a11 (i.e., the murine orthologue of human CYP3A4) mRNA expression levels compared to after three months, while γ-T3 did not increase Cyp3a11 mRNA levels [166] . Similar effects on Cyp3a protein levels were observed when 10 mg/100 g body weight of α-TOH was injected subcutaneously into rats [167] .…”

Section: Cyp3a4mentioning

confidence: 92%

“…The treatment of HepG2 cells with γ-T3 led to an up-regulation of CYP3A4 and CYP3A5 mRNA levels [169] and a dose-dependent activation of chloramphenicol acetyl transferase at 1 μmol/L to 10 μmol/L, concentrations which can be reached also in human plasma [23] . These striking contrary effects of γ-T3, up-regulation of CYP3A4 expression in vitro [168] and no effect [166] or even a reduction of Cyp3a expression [165] in vivo might be explained by different availabilities of the individual vitamin E forms at the site of action. Whereas the substance in vitro is applied onto the cells directly, all physiological processes of vitamin E handling, especially α-TTP dependent sorting of non-α-TOH forms in combination with the high metabolic degradation and elimination rates for γ-T3 [166] , may interfere in vivo, thus resulting in contradictory effects.…”

Section: Cyp3a4mentioning

confidence: 98%

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Complexity of vitamin E metabolism

Schmölz¹,

Birringer²,

Lorkowski³

et al. 2016

WJBC

183

138

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Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e. , when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their sidechain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a REVIEW

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Section: Cyp3a4mentioning

confidence: 92%

Section: Cyp3a4mentioning

confidence: 98%

Complexity of vitamin E metabolism

Schmölz¹,

Birringer²,

Lorkowski³

et al. 2016

WJBC

183

138

View full text Add to dashboard Cite

show abstract

“…Other studies showed that hepatic Cyp3a protein levels increased in mice fed an α-tocopherol sufficient diet (31 mg/kg diet) as compared with mice fed an α-tocopherol deficient diet (<2mg/kg diet) and that hepatic Cyp3a protein levels correlate with hepatic α-tocopherol levels [5]. Similarly, hepatic Cyp3a11 mRNA expression was lowest in mice fed 2 mg α-tocopherol/kg diet, increased significantly in mice fed 20 mg α-tocopherol/kg diet and further increased in mice maintained for 9 months on a diet containing 200 mg α-tocopherol/ kg [6].…”

Section: Introductionmentioning

confidence: 94%

Regulatory mechanisms to control tissue α-tocopherol

Mustacich

Elias

et al. 2007

Free Radical Biology and Medicine

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To test the hypothesis that hepatic regulation of α-tocopherol metabolism would be sufficient to prevent over-accumulation of α-tocopherol in extrahepatic tissues and that administration of high doses of α-tocopherol would up-regulate extrahepatic xenobiotic pathways, rats received daily subcutaneous injections of either vehicle or 0.5, 1, 2, or 10 mg α-tocopherol/100 g body wt for 9 days. Liver α-tocopherol increased 15-fold in rats given 10 mg α-tocopherol/100 g body weight (mg/ 100 g) compared with controls. Hepatic α-tocopherol metabolites increased with increasing α-tocopherol doses, reaching 40-fold in rats given the highest dose. In rats injected with 10 mg/100 g, lung and duodenum α-tocopherol concentrations increased 3-fold, while α-tocopherol concentrations of other extrahepatic tissues increased 2-fold or less. With the exception of muscle, daily administration of less than 2 mg/100 g) failed to increase α-tocopherol concentrations in extrahepatic tissues. Lung cytochrome P450 3A and 1A levels were unchanged by administration of α-tocopherol at any dose. In contrast, lung P-glycoprotein (MDR-1) levels increased dose dependently and expression of this xenobiotic transport protein was correlated with lung α-tocopherol concentrations (R 2 = 0.88, P < 0.05). Increased lung MDR1 may provide protection from exposure to environmental toxins by increasing alveolar space α-tocopherol.

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“…In early studies of vitamin E metabolism, CYP3A was proposed to be involved in vitamin E metabolism based on the observation that CYP3A inhibitors and stimulators altered CEHC production ( 114,(129)(130)(131). Additionally, studies in mice demonstrated that feeding ␣ -tocopherol increased cyp3a mRNA ( 132 ). However, studies in rats injected with vitamin E suggested that excess hepatic ␣ -tocopherol did not upregulate CYP4F or CYP3a ( 133 ).…”

Section: Lipoprotein Transportmentioning

confidence: 99%