Biopotencies in Rats of Several Forms of Alpha-Tocopherol

Ames, Stanley R.

doi:10.1093/jn/109.12.2198

Cited by 46 publications

(15 citation statements)

References 8 publications

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“…The zebrafish model presents an important means to elucidate the fetal requirements for α-tocopherol, independent of the maternal needs. Fetal resorption and placental failure have been noted in TTP knockout mice [4], [24], which are similar to outcomes observed upon diet-induced vitamin E deficiency [1], [25], [26]. The TTP protein is expressed in the placental and uterine cells of mice and humans [3]–[6], [27], and is thought to play an important role in supplying maternal α-tocopherol to the developing fetus to protect against oxidative stress [3].…”

Section: Discussionmentioning

confidence: 63%

The α-Tocopherol Transfer Protein Is Essential for Vertebrate Embryogenesis

et al. 2012

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The hepatic α-tocopherol transfer protein (TTP) is required for optimal α-tocopherol bioavailability in humans; mutations in the human TTPA gene result in the heritable disorder ataxia with vitamin E deficiency (AVED, OMIM #277460). TTP is also expressed in mammalian uterine and placental cells and in the human embryonic yolk-sac, underscoring TTP’s significance during fetal development. TTP and vitamin E are essential for productive pregnancy in rodents, but their precise physiological role in embryogenesis is unknown. We hypothesize that TTP is required to regulate delivery of α-tocopherol to critical target sites in the developing embryo. We tested to find if TTP is essential for proper vertebrate development, utilizing the zebrafish as a non-placental model. We verify that TTP is expressed in the adult zebrafish and its amino acid sequence is homologous to the human ortholog. We show that embryonic transcription of TTP mRNA increases >7-fold during the first 24 hours following fertilization. In situ hybridization demonstrates that Ttpa transcripts are localized in the developing brain, eyes and tail bud at 1-day post fertilization. Inhibiting TTP expression using oligonucleotide morpholinos results in severe malformations of the head and eyes in nearly all morpholino-injected embryos (88% compared with 5.6% in those injected with control morpholinos or 1.7% in non-injected embryos). We conclude that TTP is essential for early development of the vertebrate central nervous system.

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Section: Discussionmentioning

confidence: 63%

The α-Tocopherol Transfer Protein Is Essential for Vertebrate Embryogenesis

et al. 2012

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“…This finding was the basis for the “fetal resorption test” that remains in use today as an assay of biologic activities of various vitamin E forms [33]. In order to prevent fetal resorption, vitamin E must be administered to the vitamin E deficient rat mother on post-fertilization days 5 to 9 [34,35]. Interestingly, this is the same critical period where the 12/15-lipoxygenase-dependent pathway appears to mediate implantation [36].…”

Section: Discussionmentioning

confidence: 99%

Zebrafish (Danio rerio) fed vitamin E-deficient diets produce embryos with increased morphologic abnormalities and mortality

Miller¹,

Labut²,

Lebold³

et al. 2012

The Journal of Nutritional Biochemistry

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Vitamin E (α-tocopherol) is required to prevent fetal resorption in rodents. To study α–tocopherol’s role in fetal development, a non-placental model is required. Therefore, the zebrafish, an established developmental model organism, was studied by feeding the fish a defined diet with or without added α–tocopherol. Zebrafish (age: 4–6 w) were fed the deficient (E-), sufficient (E+), or lab diet up to 1 y. All groups showed similar growth rates. The exponential rate of α–tocopherol depletion up to ~80 day in E- zebrafish was 0.029 ± 0.006 nmol/g, equivalent to a depletion half-life of 25 ± 5 days. From age ~80 d, the E- fish (5 ± 3 nmol/g) contained ~50 times less α–tocopherol than the E+ or lab diet fish (369 ± 131 or 362 ± 107, respectively, P<0.05). E-depleted adults demonstrated decreased startle response suggesting neurologic deficits. Expression of selected oxidative stress and apoptosis genes from livers isolated from the zebrafish fed the three diets were evaluated by quantitative polymerase chain reaction and were not found to vary with vitamin E status. When E-depleted adults were spawned, they produced viable embryos with depleted α–tocopherol concentrations. The E- embryos exhibited a higher mortality (P<0.05) at 24 h post fertilization (hpf) and a higher combination of malformations and mortality (P<0.05) at 120 hpf than embryos from parents fed E+ or lab diets. This study documents for the first time that vitamin E is essential for normal zebrafish embryonic development.

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“…However, we reach different conclusions by reevaluating the data in those studies that present sufficient data to compare the dose-effect curves of synthetic and natural ␣-tocopherol. This re-evaluation excludes studies that did not administer sufficient dosages to obtain dose-effect curves [91], administered different dosages of natural and synthetic ␣-tocopherols [92], did not report the effects of each dose [93][94][95][96][97], or reported rejecting any data showing nonlinear or nonparallel dose-effect curves [98]. This re-evaluation includes older studies in which synthetic and natural ␣-tocopherols are designated dl-and d-␣-tocopherols, respectively, and recent studies in which synthetic and natural ␣-tocopherols are designated all-rac and RRR-␣-tocopherols, respectively.…”

Section: Discrepancies Between Studies Showing Nonconstant Relative Bmentioning

confidence: 99%