Tocotrienols have been reported to possess potent cholesterol lowering, anti-hypertensive, antiinflammatory and anti-oxidative properties which are superior to tocopherols. Emerging evidence suggests pure tocotrienols have anti-atherogenic properties. However, optimal doses of oftocotrienolrich fraction (TRF) in progressive atherogenesis remain unclear. This animal model experiment was designed to investigate the effects of a range concentration of TRF supplementation on the extent of atherosclerosis and soluble lipids, inflammatory and oxidative stress biomarkers in high-cholesterol diet (HCD) induced hypercholesterolaemic (HC) rabbits with atherosclerosis. A total of 28 New Zealand white rabbits were given 1% high-cholesterol diet (HCD) for two months and then randomised into five groups: Placebo (n=7), TRF 15 mg/kg (n=5), TRF 30 mg/kg (n=6), TRF 60 mg/kg (n=5) and TRF 90 mg/kg (n=5) daily. The treatment was given for three months and the animals were fed HCD throughout the duration. Aortic vessels were obtained to assess the extent of atherosclerotic lesions at the end of the study. Fasting serum lipids (FSL), C-reactive protein (CRP), malondialdehyde (MDA) and 8-isoprostane levels were measured at baseline, one and two months post-HCD, one, two, and three months postintervention. There were no differences in the extent of the atherosclerotic lesions, percentage changes of FSL, MDA, 8-isoprostane and CRP levels between the placebo and TRF groups. In conclusion, TRF across all doses studied have neutral effects on atherosclerotic lesions, soluble lipids, biomarkers of oxidative stress, coronary risk and inflammation in severely atherosclerotic rabbits with progressive and continuous insult by high cholesterol feeding.
Inflammation and endothelial dysfunction are key components in atherogenesis. Should the status of these pro-atherogenesis factors be enhanced during prolonged confined space travel, specific countermeasures need to be instituted to prevent these processes to ensure safe outcome for astronauts during space expeditions. Six crew members were exposed to prolonged, confined isolation for 520 days. Standard exercise and diet regime were instituted throughout isolation phase. Age and gender-matched healthy, free living controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of inflammation (hsCRP and IL-6) and endothelial activation (sICAM-1, sVCAM-1 and E-selectin). Flow-mediated dilatation (FMD) of the artery was performed following the standard protocols set by the International Brachial Artery Reactivity Task Force by trained personnel. There was decreased sVCAM-1 concentration in crew members compared to baseline. However, there was significant decrease in percentage dilatation from baseline in FMD of the brachial artery in the crew members. Percent change increment was observed in hsCRP while percent change reduction was seen in sVCAM-1. The enhanced inflammation and reduced endothelial function could possibly be attributed to the rigorous exercise instituted throughout the confinement period. Furthermore, possible haemoconcentration as a result of psychosocial stress and/ or exercise-induced physiological response could further explain elevations in hsCRP, and unlikely pathological. Furthermore, endothelial activation was attenuated during isolation, suggesting that the diet and exercise program instated throughout the period improved endothelial function.