Efficacy of topically applied tocopherols and tocotrienols in protection of murine skin from oxidative damage induced by UV-irradiation

Weber C, Podda M, Rallis M, Thiele JJ, Traber MG, Packer L.

Free Radic Biol Med. 1997;22(5):761-9.

To assess the efficacy of various forms of vitamin E in protection of skin from UV-light-induced oxidative stress, vitamin E (tocotrienol-rich fraction of palm oil, TRF) was applied to mouse skin and the contents of antioxidants before and after exposure to UV-light were measured. Four polypropylene plastic rings (1 cm2) were glued onto the animals’ backs, and 20 microliters 5% TRF in polyethylene glycol-400 (PEG) was applied to the skin circumscribed by two rings and 20 microliters PEG to the other two rings. After 2 h, the skin was washed and half of the sites were exposed to UV-irradiation (2.8 mW/cm2 for 29 mi: 3 MED). TRF treatment (n = 19 mice) increased mouse skin alpha-tocopherol 28 +/- 16-fold, alpha-tocotrienol 80 +/- 50-fold, gamma-tocopherol 130 +/- 108-fold, and gamma-tocotrienol 51 +/- 36-fold. A significantly higher percentage of alpha-tocopherol was present in the skin as compared with that in the applied TRF. After UV-irradiation, all vitamin E forms decreased significantly (p < .01), while a larger proportion of the vitamin E remained in PEG-treated (approximately 80%) compared with TRF-treated (approximately 40%) skin. Nonetheless, vitamin E concentrations in irradiated TRF-treated skin were significantly higher than in the nonirradiated PEG-treated (control) skin (p < .01). Thus, UV-irradiation of skin destroys its antioxidants: however, prior application of TRF to mouse skin results in preservation of vitamin E.

This study was undertaken to assess the effect of blended oils, i.e., polyunsaturated fatty acid (PUFA) rich vegetable oils like safflower oil (SFO) and sunflower oil (SNO) with the unconventional and hypocholesterolemic rice bran oil (RBO) on the serum lipid profile of rats. Rats fed RBO+SNO/SFO at 70:30 ratio for a period of 28 days showed significantly (p < 0.05) lower levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) cholesterol and increased high density lipoprotein (HDL) cholesterol in animals fed a high cholesterol diet (HCD) and cholesterol free diet (CFD). Liver total cholesterol (TC) and triglycerides (TG) were also reduced. Fecal excretion of neutral sterols and bile acids was increased with use of RBO blends. RBO, which is rich in tocopherols and tocotrienols, may improve the oxidative stability of the blends. Tocotrienols are known to inhibit 3-hydroxy, 3-methyl, glutaryl CoA (HMG-COA) reductase (rate limiting enzyme in cholesterol biosynthesis), resulting in hypocholesterolemia. In addition to improving the lipid profile by lowering TC, TG and LDL-C and increasing HDL-C, blending of RBO with other oils can result in an economic advantage of lower prices.

Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells by palm oil tocotrienols and tamoxifen, alone and in combination

Guthrie, N.,Gapor, A.,Chambers, A. F.,Carroll, K. K.

J Nutr, 1997;127(3):544S-548S

Tocotrienols are a form of vitamin E, having an unsaturated isoprenoid side-chain rather than the saturated side-chain of tocopherols. The tocotrienol-rich fraction (TRF) from palm oil contains alpha-tocopherol and a mixture of alpha-, gamma- and delta-tocotrienols. Earlier studies have shown that tocotrienols display anticancer activity. We previously reported that TRF, alpha-, gamma- and delta-tocotrienols inhibited proliferation of estrogen receptor-negative MDA-MB-435 human breast cancer cells with 50% inhibitory concentrations (IC50) of 180, 90, 30 and 90 microg/mL, respectively, whereas alpha-tocopherol had no effect at concentrations up to 500 microg/mL. Further experiments with estrogen receptor-positive MCF-7 cells showed that tocotrienols also inhibited their proliferation, as measured by [3H] thymidine incorporation. The IC50s for TRF, alpha-tocopherol, alpha-, gamma- and delta-tocotrienols were 4, 125, 6, 2 and 2 microg/mL, respectively. Tamoxifen, a widely used synthetic antiestrogen inhibits the growth of MCF-7 cells with an IC50 of 0.04 microg/mL. We tested 1:1 combinations of TRF, alpha-tocopherol and the individual tocotrienols with tamoxifen in both cell lines. In the MDA-MB-435 cells, all of the combinations were found to be synergistic. In the MCF-7 cells, only 1:1 combinations of gamma- or delta-tocotrienol with tamoxifen showed a synergistic inhibitory effect on the proliferative rate and growth of the cells. The inhibition by tocotrienols was not overcome by addition of excess estradiol to the medium. These results suggest that tocotrienols are effective inhibitors of both estrogen receptor-negative and -positive cells and that combinations with tamoxifen should be considered as a possible improvement in breast cancer therapy.

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