Tocotrienol-Rich Tocomin Attenuates Oxidative Stress and Improves Endothelium-Dependent Relaxation in Aortae from Rats Fed a High-Fat Western Diet

Abstract

We have previously reported that tocomin, a mixture high in tocotrienol content and also containing tocopherol, acutely preserves endothelial function in the presence of oxidative stress. In this study, we investigated whether tocomin treatment would preserve endothelial function in aortae isolated from rats fed a high-fat diet known to cause oxidative stress. Wistar hooded rats were fed a western diet (WD, 21% fat) or control rat chow (standard diet, 6% fat) for 12 weeks. Tocomin (40 mg/kg/day sc) or its vehicle (peanut oil) was administered for the last 4 weeks of the feeding regime. Aortae from WD rats showed an impairment of endothelium-dependent relaxation that was associated with an increased expression of the NADPH oxidase Nox2 subunit and an increase in the vascular generation of superoxide measured using L-012 chemiluminescence. The increase in vascular oxidative stress was accompanied by a decrease in basal NO release and impairment of the contribution of NO to ACh-induced relaxation. The impaired relaxation is likely contributed to by a decreased expression of eNOS, calmodulin, and phosphorylated Akt and an increase in caveolin. Tocotrienol rich tocomin, which prevented the diet-induced changes in vascular function, reduced vascular superoxide production and abolished the diet-induced changes in eNOS and other protein expression. Using selective inhibitors of nitric oxide synthase (NOS), soluble guanylate cyclase (sGC) and calcium-activated potassium (KCa) channels we demonstrated that tocomin increased NO-mediated relaxation, without affecting the contribution of endothelium-dependent hyperpolarization type relaxation to the endothelium-dependent relaxation. The beneficial actions of tocomin in this diet-induced model of obesity suggest that it may have potential to be used as a therapeutic agent to prevent vascular disease in obesity.

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

“…The anti-obesity effects of T3 have also been demonstrated in in vitro studies [331][332][333] and obese animal models [41,102,103,314,316,334]. T3 suppressed adipogenesis with the decrease of intracellular TG level and lipid droplets in mouse hepatoma Hepa 1-6 cells [40], human hepatoma HepG2 cells [41,47], 3T3-L1 murine preadipocytes [331,335], 3T3-F442A murine preadipocytes [336], and primary human adipose-derived stem cells [317,332].…”

“…In like manner, δT3 did not possess any direct antidiabetic activity where it only weakly reduced the accumulation of AGEs in a cell-free anti-AGEs assay [344]. On the other hand, T3 supplement, Tocomin ® was unable to improve glycemic control in obese rats [334,345]. This might due to the composition of Tocomin ® and the stable glycemic status of these rats [334].…”

“…Oral administration of Tocomin ® [334], palm TRF [102], γT3 and δT3 (but not αT3) [103] significantly improved the cardiovascular function of obese rodents by normalizing the systolic BP, improving the systolic function and contractile response, and reducing myocardial inflammation. Besides, T3 was showed to reduce cardiovascular complications in diabetic animals by protecting the thoracic aorta of diabetic rats from vascular wall alterations and degeneration [58].…”

“…On the other hand, T3 supplement, Tocomin ® was unable to improve glycemic control in obese rats [334,345]. This might due to the composition of Tocomin ® and the stable glycemic status of these rats [334].…”

Naringin ameliorates endothelial dysfunction in fructose-fed rats

“…As previously described (27), after the removal of superficial connective tissue and fat surrounding the aorta, the isolated thoracic aorta was cut into rings (3-4 mm in length) and mounted on stainless steel hooks in an organ bath chamber containing oxygenated Krebs bicarbonate solution (95% O 2 and 5% CO 2 ) maintained at 37˚C. The isometric tension of aortic ring was recorded using a force transducer (model no.…”