Effect of tocopheryl phosphate on key biomarkers of inflammation: Implication in the reduction of atherosclerosis progression in a hypercholesterolaemic rabbit model

Abstract

1. Many studies have evaluated the effectiveness of alpha-tocopherol (vitamin E) in the development and progression of cardiovascular diseases, with conflicting results reported on the protective effect of this anti-oxidant. 2. The present study examined the effectiveness of a novel tocopheryl phosphate mixture (TPm) compared with that of alpha-tocopherol (TA) on key pro-inflammatory markers involved in atherogenesis, including interleukin (IL)-1beta, IL-6, IL-8, plasminogen activator inhibitor-1, tumour necrosis factor-alpha and C-reactive protein (CRP), as well as vascular function and lesion development in rabbits fed a 2% cholesterol diet. 3. Treatment with TPm, incorporated into the rabbit food at four doses ranging from 60 to 360 mg/kg chow, resulted in a significant reduction in plasma levels of all pro-inflammatory cytokines and biomarkers that appeared to be somewhat dose dependent. Conversely, treatment with TA, at a dose equivalent to the highest dose of TPm used, only decreased plasma levels of CRP, IL-6 and IL-8. Both TPm and TA treatment significantly improved vascular function to a similar extent, although TPm was more effective in reducing lesion development. 4. The reduction in these key pro-inflammatory markers appears to follow the improvement in the atherogenic state of the animals, indicating that the anti-inflammatory properties of TPm may be potentially beneficial in inflammatory disease states.

Inhibitory Effects of Different Forms of Tocopherols, Tocopherol Phosphates, and Tocopherol Quinones on Growth of Colon Cancer Cells

“…α-TP is converted to α-T in cultured cells and in mice, although it is still not clear which phosphatase is responsible for this process 35 . Intact α-TP has been proposed to function as a signaling messenger; for example, it reduces the production of proinflammatory cytokines 36 . The studies of other forms of TP are rather limited.…”

Modulation of Phosphorylation of Tocopherol and Phosphatidylinositol by hTAP1/SEC14L2-Mediated Lipid Exchange

“…αTP may act as an active cofactor for specific enzymatic reactions (reviewed in [9]), it may be a ligand of a receptor or transcription factor, or act as “second messenger” in the membrane capable of exerting regulatory effects [2]. In vivo , atherosclerotic lesions of hypercholesterolemic rabbits are more efficiently reduced by supplementation with αTP when compared to α-tocopheryl acetate (αTA), resulting from reduced cytokines and scavenger receptor expression [10], [11]. The often higher potency of αTP when compared to αT is either due to a better uptake and cellular retention of the molecule e.g.…”

Vitamin E: A Role in Signal Transduction

“…Similarly, the inhibitory effects of thrombospondin on angiogenesis-effects that are mediated by CD36-could be influenced by vitamin E by changing the presence and activity of CD36 at the plasma membrane (43). Since CD36 has been recently implicated in coordinating intracellular cholesterol crystal formation leading to NLPR3 inflammasome activation and induction of IL-1β expression (215a), a reduction of CD36 at the cellular surface by αTP may also explain the anti-inflammatory effects of αTP in hypercholesterolemic rabbits (128).…”

“…The induction of VEGF expression by αTP suggests that it may be involved in angiogenesis and vasculogenesis (reviewed in 280). In vivo, αTP reduces atherosclerotic lesions as result of lower expression of cytokines and CD36 scavenger receptor in hypercholesterolemic rabbits (128,164).…”