VITAMIN E (d-ALPHA TOCOPHERYL SUCCINATE)
Protective effects of vitamin E forms (alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate) on retinal edema during ischemia-reperfusion injury in the guinea pig retina
1: Int Ophthalmol. 2004 Oct-Dec;25(5-6):283-9. Epub 2006 Mar 7
Protective effects of vitamin E forms (alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate) on retinal edema during ischemia-reperfusion injury in the guinea pig retina.
Department of Ophthalmology, School of Medicine, Firat Unv Tip Fak Goz Hast AD, Elazig, Turkey. orhanaydemir23@yahoo.com
PURPOSE: The purpose of this study is to provide evidence that free radical damage is a component of retinal ischemia-reperfusion (I/R) injury, and to determine whether alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) can protect the retina from this injury. METHODS: The right eyes of 40 male guinea pigs weighing 500-600 g were used. The animals were randomly assigned to group 1 (control), group 2 (I/R), group 3 (I/R plus alpha-tocopherol), group 4 (I/R plus gamma-tocopherol) and group 5 (I/R plus TPGS). Groups 3, 4 and 5 received four subcutaneous injections at six-hour intervals for total dosage of 800 IU/kg alpha-tocopherol, 1000 IU/kg gamma-tocopherol and 750 IU/kg TPGS, respectively. The first dose of each substance was administered 5 minutes before retinal ischemia. Retinal ischemia was induced for 90 minutes, then followed by reperfusion for 24 hours. Injections of three substances were repeated at 6, 12 and 18 hours during reperfusion. The animals were killed at 24 hours of reperfusion. Sagittal sections of 4 microm were cut and stained with hematoxylin and eosin for light microscopic evaluation. The average thickness (edema) of the inner plexiform layer for each eye was measured in sagittal sections near the optic nerve and expressed in microns. RESULTS: All the three substances showed statistically significant protection against the formation of retinal edema during ischemia-reperfusion injury. The mean thickness of the inner plexiform layer were 15.0, 25.44, 19.81, 21.38 and 20.88 microm in control, I/R, I/R plus alpha-tocopherol, I/R plus gamma-tocopherol and I/R plus TPGS groups, respectively. The results showed that the thickness of the inner plexiform layer in group 1 (control) was significantly lower than the other groups (p<0.001). The inner plexiform layer was thicker in the I/R group than with I/R plus alpha-tocopherol (p<0.001), I/R plus gamma-tocopherol (p<0.001) and I/R plus TPGS (p<0.01). The inner plexiform layer was not thicker in the I/R plus TPGS group than in the I/R plus alpha-tocopherol and I/R plus gamma-tocopherol groups. Compared to the I/R plus alpha-tocopherol group, the inner plexiform layer was significantly thicker in the I/R plus gamma-tocopherol group (p<0.01). CONCLUSIONS: The results from these experiments indicate that vitamin E forms have protective effects on the retina during retinal ischemia-reperfusion injury, but, the effects of alpha-tocopherol and TPGS appear to be much greater than that of gamma-tocopherol.
PMID: 16532291 [PubMed - indexed for MEDLINE]
Antioxidant effects of alpha-, gamma- and succinate-tocopherols in guinea pig retina during ischemia-reperfusion injury
: Pathophysiology. 2004 Dec;11(3):167-171
Antioxidant effects of alpha-, gamma- and succinate-tocopherols in guinea pig retina during ischemia-reperfusion injury.
Department of Ophthalmology, Medical Faculty, Firat University, Elazig TR-23119, Turkey.
The purpose of this study is to investigate the efficacy of alpha-tocopherol (AT), gamma-tocopherol (GT) and d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) in preventing the retinal injury followed by ischemia-reperfusion (IR). The eyes of 40 adult male guinea pigs were used in the study. The guinea pigs were divided into five groups of eight rats each. First and second groups were used as control and IR groups, respectively. Third, fourth and fifth groups received subcutaneously AT, GT and TPGS, respectively. Treatment with each vitamin was performed before 5min of ischemia with reperfusion at 6h intervals for three times. Retinal ischemia was induced for 90min, then followed by reperfusion for 24h. The animals were killed at 24h of reperfusion. Lipid peroxidation (LP) and glutathione (GSH) levels were measured in right retinas by using a spectrofluorometer. Retinal GSH levels were found significantly lower (p < 0.002) in the IR group than in control group and there was a significant increase in the LP levels in IR group (p < 0.001). The decrease of GSH and increase of LP levels in the IR animals were significantly (p < 0.05 and 0.001) improved by the administration of the Vitamin E forms. When compared to GT group, there were no significant differences in LP levels in AT and TPGS groups. However, LP level in AT group was significantly (p < 0.01) lower than in the TPGS group. The GSH levels were higher (p < 0.001) in AT and TPGS groups than in IR group. Therefore, modulator effect of AT and GT were greater than that of TPGS. In conclusion, present data demonstrate that there is an increase in the LP in the retina of IR-induced animals and a decrease in the GSH levels. However, subcutaneous AT, GT and TPGS were effective in preventing retinal injury followed by ischemia-reperfusion. The subcutaneous AT may play a role in treating IR injury.
PMID: 15561514 [PubMed - as supplied by publisher]
Vitamin E therapy in Parkinson's disease
: Toxicology. 2003 Jul 15;189(1-2):129-46.
Vitamin E therapy in Parkinson's disease.
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164-6534, USA. fariss@mail.wsu.edu
Though the etiology is not well understood, late-onset Parkinson's disease (PD) appears to result from several key factors including exposure to unknown environmental toxicants, toxic endogenous compounds and genetic alterations. A plethora of scientific evidence suggest that these environmental and endogenous factors cause PD by producing mitochondrial (mito) oxidative stress and damage in the substantia nigra, leading to cell death. Thus assuming a critical role for mito oxidative stress in PD, therapies to treat or prevent PD must target these mito and protect them against oxidative damage. The focus of this article is to briefly review the experimental and clinical evidence for the role of environmental toxicants and mito oxidative stress/damage in PD as well as discuss the potential protective role of mito d-alpha-tocopherol (T) enrichment and vitamin E therapy in PD. New experimental data are presented that supports the enrichment of mito with T as a critical event in cytoprotection against toxic mito-derived oxidative stress. We propose that chronic, high dose vitamin E dietary supplementation or parenteral vitamin E administration (e.g. vitamin E succinate) may serve as a successful therapeutic strategy for the prevention or treatment of PD (by enriching substantia nigra mito with protective levels of T).
PMID: 12821288 [PubMed - indexed for MEDLINE]
D-alpha-tocopheryl succinate (vitamin E) enhances radiation-induced chromosomal damage levels in human cancer cells, but reduces it in normal cells
1: J Am Coll Nutr. 2002 Aug;21(4):339-43.
D-alpha-tocopheryl succinate (vitamin E) enhances radiation-induced chromosomal damage levels in human cancer cells, but reduces it in normal cells.
Center for Vitamins and Cancer Research, Department of Radiology, University of Colorado Health Sciences Center, Denver 80262-0278, USA.
OBJECTIVE: The purpose of this study was to measure and compare the effect of d-alpha-tocopheryl succinate (alpha-TS) in modifying radiation-induced chromosomal damage in human normal cells and cancer cells in culture. METHODS: Three human normal fibroblast cell lines (GM2149, AG1522 and HF19) and three human cancer cell lines, cervical cancer (HeLa) and ovarian carcinoma cells (OVGI and SKOV3) were treated with alpha-TS (37.6 microM) 20 hours before 100 cGy gamma-irradiation. After 30 minutes of irradiation, colcemid was added and cells were fixed. One hundred randomly selected metaphase cells were scored for the presence of chromatid gaps and breaks. To study the cellular accumulation of alpha-TS. cells were incubated in the presence of alpha-TS (18.8 and 37.6 microM) for 24 hours, and alpha-TS was extracted with hexane using a-tocopheryl acetate as an internal standard. The levels of alpha-TS were determined by HPLC. RESULTS: Results showed that alpha-TS induced chromosomal damage in both human cervical cancer cells and ovarian cancer cells, but not in human normal fibroblasts in culture. In addition, alpha-TS enhanced the level of radiation-induced chromosomal damage in cancer cells, but it protected normal cells against such damage. Both cancer cells and normal cells accumulated similar levels of alpha-TS, suggesting that increased sensitivity of cancer cells to alpha-TS is acquired during transformation. CONCLUSION: The use of alpha-TS during radiation therapy may improve the efficacy of radiation therapy by enhancing tumor response and decreasing some of the toxicities on normal cells.
PMID: 12166531 [PubMed - indexed for MEDLINE]
Vitamin E and breast cancer
1: J Nutr. 2004 Dec;134(12 Suppl):3458S-3462S.
Vitamin E and breast cancer.
Division of Nutrition and School of Biological Sciences, University of Texas at Austin, Austin, TX 78712, USA. k.kline@mail.utexas.edu
Vitamin E is a term that describes a group of compounds with similar yet unique chemical structures and biological activities. One interesting property possessed by certain vitamin E compounds-namely, delta-tocotrienol, RRR-alpha-tocopheryl succinate [vitamin E succinate (VES), a hydrolyzable ester-linked succinic acid analogue of RRR-alpha-tocopherol], and a novel vitamin E analogue referred to as alpha-TEA (alpha-tocopherol ether linked acetic acid analogue, which is a stable nonhydrolyzable analogue of RRR-alpha-tocopherol)-is their ability to induce cancer cells but not normal cells to undergo a form of cell death called apoptosis. In contrast, the parent compound, RRR-alpha-tocopherol, also referred to as natural or authentic vitamin E and known for its antioxidant properties, does not induce cancer-cell apoptosis. Efforts to understand how select vitamin E forms can induce cancer cells to undergo apoptosis have identified several nonantioxidant biological functions, including restoration of pro-death transforming growth factor-beta and Fas signaling pathways. Recent studies with alpha-TEA show it to be a potent inducer of apoptosis in a wide variety of epithelial cancer cell types, including breast, prostate, lung, colon, ovarian, cervical, and endometrial in cell culture, and to be effective in significantly reducing tumor burden and metastasis in a syngeneic mouse mammary tumor model, as well as xenografts of human breast cancer cells. Studies also show that alpha-TEA, in combination with the cyclooxygenase-2 inhibitor celecoxib and the chemotherapeutic drug 9-nitro-camptothecin decreases breast cancer animal model tumor burden and inhibits metastasis significantly better than do single-agent treatments.
PMID: 15570054 [PubMed - indexed for MEDLINE]
Enhanced antioxidant and cytoprotective abilities of vitamin E succinate is associated with a rapid uptake advantage in rat hepatocytes and mitochondria
: Free Radic Biol Med. 2001 Aug 15;31(4):530-41.
Enhanced antioxidant and cytoprotective abilities of vitamin E succinate is associated with a rapid uptake advantage in rat hepatocytes and mitochondria.
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164-6534, USA. fariss@wsu.edu
Numerous in vitro studies attest to the enhanced ability of vitamin E succinate (TS), as compared with conventional vitamin E compounds such as unesterified d-alpha-tocopherol (T) and d-alpha-tocopheryl acetate (TA), to protect hepatocytes from toxic oxidative stress. In the present study we tested the hypothesis that this unique protective ability is related to an enhanced cellular accumulation of TS. The results of this study indicate, using both in vitro and in vivo model systems, that acute TS administration results in a rapid increase in T and TS content and antioxidant protection of hepatocytes and mitochondria. In contrast, conventional vitamin E compounds such as T and TA lack these same protective properties. We suggest that TS acts as a unique delivery system for T, rapidly accumulating in cellular and mitochondrial membranes and gradually releasing active T to prevent membrane oxidative damage. We propose that TS administration may prove useful for the prevention and treatment of oxidative stress-mediated diseases, especially those of mitochondrial origin.
PMID: 11498286 [PubMed - indexed for MEDLINE]
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