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

Abstract

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.

Revisiting the therapeutic potential of tocotrienol

“…The same study also showed superior antioxidant effects of the tocopherols compared to the tocotrienol counterparts. 310 The metabolism of both tocopherol and tocotrienols undergo a similar process although the tocotrienols degrade in a more complex manner. In vitro differences have been observed in a HepG2 cell culture model although it was postulated to be different in in vivo systems.…”

Anandamide Alters Barrier Integrity of Bovine Vascular Endothelial Cells during Endotoxin Challenge

“…Elevated IsoP production is an indicator for oxidative stress, or damage to healthy tissue by free radicals, such as ROS. Even though the effect of IsoP on bovine vascular endothelial cells remains elusive [ 22 ], increased ROS production is associated with endothelial dysfunction [ 23 ]. Elevated IsoP production associated with addition of 1 and 5 µM AEA may therefore be a key contributor to decreased TER observed at these concentrations.…”

Protective Effects of Coadministration of the Vitamin E and Omega-3 on Doxorubicin-Induced Hepatotoxicity in Mice

“…Vit E can decrease ischemia-reperfusion tissue damage (26). Some investigators have shown that small vessels' killed endothelium will enhance after the Vit E regime (27,28). Vit E regime therapy controls neoplasms growth and protects against chemotherapic side effects (29).…”