Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824.
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824.
J Dairy Sci. 2021 Jun;104(6):7154-7167. doi: 10.3168/jds.2020-19675. Epub 2021 Mar 25.
Diseases that occur during the transition period are exacerbated when cows are unable to cope with an increased pro-oxidant load that results in oxidative stress. Dairy cattle are routinely supplemented with the vitamin E analog α-tocopherol to mitigate the severity of oxidative stress. Nonetheless, oxidative stress remains a disease predisposing condition for many dairy cattle. A better method of optimizing the antioxidant functions of vitamin E is needed. α-Tocopherol is only 1 of 8 analogs of vitamin E, all of which have varying antioxidant properties in other mammals, albeit a shorter physiological half-life compared with α-tocopherol. A primary bovine mammary endothelial cell oxidant challenge model was used to determine functions of certain vitamin E analogs. The aim of this study was to determine if other analogs, namely γ-tocopherol or γ-tocotrienol, have antioxidative functions in bovine cells and if these functions may protect cellular viability and endothelial function from oxidant damage. Physiological (10 μM) and supraphysiological (50 μM) concentrations of γ-tocopherol and γ-tocotrienol had a greater capacity to reduce accumulated reactive oxygen species derived from a nitric oxide donating pro-oxidant antagonist, when compared with α-tocopherol, after 30 min to 6 h of treatment. Further, γ-tocotrienol (10 μM) decreased cell cytotoxicity to a greater amount than other analogs at like concentrations, whereas γ-tocopherol (10 μM) reduced lipid peroxidation and apoptosis more effectively than other analogs. Last, α-tocopherol (5 and 10 μM) and γ-tocopherol (5 and 10 μM) significantly slowed pro-oxidant induced loss of endothelial cell barrier integrity over a 48-h period using an electrical cell-substrate impedance sensing system. Concerningly, γ-tocotrienol drastically reduced the endothelial barrier integrity at only 5 μM despite no apparent effect on cellular viability at like concentrations. γ-Tocotrienol, however, was also the only analog to show significant cytotoxicity and reductions in viability at supraphysiological doses (25 and 50 μM). Our results suggest that γ-tocopherol has antioxidant activities that reduces cellular damage and loss of function due to oxidant challenge as effectively as α-tocopherol. These data set the foundation for further investigation into the antioxidant properties of vitamin E analogs in other bovine cells types or whole animal models.
当奶牛无法应对增加的促氧化剂负荷导致氧化应激时，过渡期间发生的疾病会加剧。奶牛通常会补充维生素 E 类似物α-生育酚以减轻氧化应激的严重程度。尽管如此，氧化应激仍然是许多奶牛的一种易患疾病的条件。需要一种更好的方法来优化维生素 E 的抗氧化功能。α-生育酚只是维生素 E 的 8 种类似物之一，所有这些类似物在其他哺乳动物中都具有不同的抗氧化特性，尽管与α-生育酚相比，它们的生理半衰期较短。使用主要的牛乳腺内皮细胞氧化剂挑战模型来确定某些维生素 E 类似物的功能。本研究的目的是确定其他类似物，即γ-生育酚或γ-生育三烯酚，是否在牛细胞中具有抗氧化功能，以及这些功能是否可以保护细胞活力和内皮功能免受氧化剂损伤。与α-生育酚相比，生理（10 μM）和超生理（50 μM）浓度的γ-生育酚和γ-生育三烯酚在 30 分钟至 6 小时的治疗后，具有更大的能力来减少来自一氧化氮供体促氧化剂拮抗剂的累积活性氧。此外，与其他类似物相比，γ-生育三烯酚（10 μM）在相同浓度下降低细胞细胞毒性的量更大，而γ-生育酚（10 μM）比其他类似物更有效地减少脂质过氧化和细胞凋亡。最后，α-生育酚（5 和 10 μM）和γ-生育酚（5 和 10 μM）在 48 小时期间使用电细胞-底物阻抗传感系统显著减缓了促氧化剂诱导的内皮细胞屏障完整性丧失。令人担忧的是，γ-生育三烯酚尽管在相同浓度下对细胞活力没有明显影响，但仅在 5 μM 时就大大降低了内皮屏障完整性。然而，γ-生育三烯酚也是唯一一种在超生理剂量（25 和 50 μM）下表现出显著细胞毒性和活力降低的类似物。我们的结果表明，γ-生育酚具有抗氧化活性，可有效减少因氧化剂挑战而导致的细胞损伤和功能丧失，与α-生育酚一样有效。这些数据为进一步研究维生素 E 类似物在其他牛细胞类型或整个动物模型中的抗氧化特性奠定了基础。
