Vitamin E analogs limit in vitro oxidant damage to bovine mammary endothelial cells

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 alpha-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. alpha-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 alpha-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 gamma-tocopherol or gamma-tocotrienol, have antioxidative functions in bovine cells and if these functions may protect cellular viability and endothelial function from oxidant damage. Physiological (10 mu M) and supraphysiological (50 mu M) concentrations of gamma-tocopherol and gamma-tocotrienol had a greater capacity to reduce accumulated reactive oxygen species derived from a nitric oxide donating pro-oxidant antagonist, when compared with alpha-tocopherol, after 30 min to 6 h of treatment. Further, gamma-tocotrienol (10 mu M) decreased cell cytotoxicity to a greater amount than other analogs at like concentrations, whereas gamma-tocopherol (10 mu M) reduced lipid peroxidation and apoptosis more effectively than other analogs. Last, alpha-tocopherol (5 and 10 mu M) and gamma-tocopherol (5 and 10 mu M) 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, gamma-tocotrienol drastically reduced the endothelial barrier integrity at only 5 mu M despite no apparent effect on cellular viability at like concentrations. gamma-Tocotrienol, however, was also the only analog to show significant cytotoxicity and reductions in viability at supraphysiological doses (25 and 50 mu M). Our results suggest that gamma-tocopherol has antioxidant activities that reduces cellular damage and loss of function due to oxidant challenge as effectively as alpha-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.

Automated summary

This study explored the antioxidant functions of various vitamin E analogs in bovine cells, finding that gamma-tocopherol and gamma-tocotrienol may have better abilities to reduce oxidative stress and protect cellular viability compared to alpha-tocopherol. Gamma-tocotrienol was shown to have significant cytotoxicity and reductions in viability at higher doses, suggesting a potential negative impact at supraphysiological levels. Further research is needed to fully understand the antioxidant properties of different vitamin E analogs in different cell types or animal models.