title: Diet-derived and topically applied tocotrienols accumulate in skin and protect the tissue against ultraviolet light-induced oxidative stress.
abstract: To evaluate the tissue-specific distribution of lipophilic antioxidants including various vitamin E forms (tocotrienols and tocopherols) and oxidised and reduced coenzyme Q (ubiquinone and ubiquinol), a sensitive procedure was developed using gradient HPLC with both electrochemical- and UV-detection. A unique distribution of these antioxidants in hairless mouse tissues was found, suggesting that their distribution may be dependent upon selective mechanisms for maintaining antioxidant defences. Ubiquinol-9 was highest in kidney (81 ± 29 nmol/g) and in liver (42 ± 16 nmol/g), while the highest ubiquinone-9 concentrations were found in kidney (301 ± 123 nmol/g) and heart (244 ± 22 nmol/g). Liver contained nearly identical amounts of each ubiquinol-9 (41 ± 16 nmol/g) and ubiquinone-9 (46 ± 18 nmol/g). These mice were fed a commercial chow diet containing α-tocopherol (30 ± 6 mg/kg diet), γ-tocopherol (10 ± 1), a-tocotrienol (3.1 ± 0.7) and γ-tocotrienol (7.4 ± 1.7). Of the vitamin E forms, brain contained only α-tocopherol (5.4 ± 0.1 nmol/g; 99.8%) and no detectable tocotrienols. In other tissues, the α-tocopherol content was higher (20 nmol/g), while each of the other forms represented about 1 % of the total ( γ-tocopherol 0.2 to 0.4 nmol/g, a-tocotrienol 0.1, γ-tocotrienol 0.2). Remarkably, skin contained nearly 15% tocotrienols and 1% γ-tocopherol. The unique distribution of tocotrienols in skin suggested that they might have superior protection against environment stressors. Therefore, the penetration of topically applied vitamin E (tocotrienol enriched fraction of palm oil, TRF) and vitamin E homologue concentrations before and after exposure of skin to UV-light was assessed. 20 μL of 5% TRF in polyethylene glycol-400 (PEG) was applied to 2 skin sites and 20 μL PEG to 2 other sites. After 2 h, the skin was washed and half of the sites exposed to UV-irradiation using a solar simulator (2.8 mW/cm2 for 29 min). The vitamin E content of hairless mouse skin was: α-tocopherol 9.0 ± 1.0 nmol/g skin, γ-tocopherol 0.44 ± 0.03, a-tocotrienol 0.48 ± 0.07, γ-tocotrienol 0.92 ± 0.03. Topical TRF enriched skin vitamin E: α-tocopherol 201 ± 70 nmol/g skin, γ-tocopherol 37 ± 15, a-tocotrienol 53 ± 25, and γ-tocotrienol 50 ± 24. After UV-irradiation, concentrations of all vitamin E homologues from both treatment areas decreased significantly (p<0.01), but the TRF-treated skin contained vitamin E at concentrations 7- to 30-fold higher than control values. These findings provide provocative clues on the uptake and regulation of tissue lipophilic antioxidants. The unique distribution of these antioxidant substances suggests their distribution may be dependent upon tissue-specific selective mechanisms.
authors.affiliation: Dept. Molecular and Cell Biology, University of California, Berkeley.
authors.forename: M G
authors.initials: MG
authors.lastname: Traber
authors.forename: M
authors.initials: M
authors.lastname: Podda
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.forename: J
authors.initials: J
authors.lastname: Thiele
authors.forename: M
authors.initials: M
authors.lastname: Rallis
authors.forename: L
authors.initials: L
authors.lastname: Packer