Andreas M. Papas

Determinants of antioxidant status in humans

Antioxidant status in humans reflects the dynamic balance between the antioxidant system and prooxidants and has been suggested as a useful tool in estimating the risk of oxidative damage. This paper reviews determinants of antioxidant status such as diet including antioxidant nutrient and nonnutrient intake, absorption and bioavailabilty, dietary components such as polyunsaturated fatty acids and transition metals, food storage and processing, chemical form, chirality and formulation of supplemental compounds and alcohol intake; environmental factors such as pollutants, ultraviolet radiation and smoking; injury and disease, medications and other medical treatments such as radiation; strenuous exercise; and physiological stage or conditions such as those in premature babies and the elderly. It is proposed that, in addition to current focus on tissues, the antioxidant status of digesta should be considered because of its effect on specific tissues and potential health implications.

Rumen-stable delivery systems

Ruminants have a distinct digestive system which serves a unique symbiotic relationship between the host animal and predominantly anaerobic rumen bacteria and protozoa. Rumen fermentation can be both beneficial by enabling utilization of cellulose and non-protein nitrogen and detrimental by reducing the nutritive value of some carbohydrates, high biological value proteins and by hydrogenating unsaturated lipids. In addition it can also result in the modification and inactivation of many pharmacologically active ingredients administered to the host animal via the oral route. The advances in ruminant nutrition and health demand a rumen-stable delivery system which can deliver the active ingredient post-ruminally while simultaneously meet efficacy, safety and cost criteria. In contrast to drug delivery systems for humans, the demand for low-cost has hindered the development of effective rumen-stable delivery systems. Historically, heat and chemical treatment of feed components, low solubility analogues or lipid-based formulations have been used to achieve some degree of rumen-stability, and products have been developed accordingly. Recently, a polymeric pH-dependent rumen-stable delivery system has been developed and commercialized. The rationale of this delivery system is based on the pH difference between ruminal and abomasal fluids. The delivery system is composed of a basic polymer, a hydrophobic substance and a pigment material. It can be applied as a coating to solid particles via a common encapsulation method such as air-suspension coating. In the future, the delivery system could be used to deliver micronutrients and pharmaceuticals post-ruminally to ruminant animals. A further possible application of the delivery system is that it could also be combined with other controlled delivery devices/systems in order to enhance slow release or to achieve targeted delivery needs for ruminants. This paper discusses the rumen protection and the abomasal release mechanism of the polymeric coating. It also reviews other rumen stable delivery systems and methods for evaluating their in vitro and in vivo performance.

The uptake of tocopherols by RAW 264.7 macrophages

BackgroundAlpha-Tocopherol and gamma-tocopherol are the two major forms of vitamin E in human plasma and the primary lipid soluble antioxidants. The dietary intake of gamma-tocopherol is generally higher than that of alpha-tocopherol. However, alpha-tocopherol plasma levels are about four fold higher than those of gamma-tocopherol. Among other factors, a preferential cellular uptake of gamma-tocopherol over alpha-tocopherol could contribute to the observed higher plasma alpha-tocopherol levels. In this investigation, we studied the uptake and depletion of both alpha-tocopherol and gamma-tocopherol (separately and together) in cultured RAW 264.7 macrophages. Similar studies were performed with alpha-tocopheryl quinone and gamma-tocopheryl quinone, which are oxidation products of tocopherols.ResultsRAW 264.7 macrophages showed a greater uptake of gamma-tocopherol compared to alpha-tocopherol (with uptake being defined as the net difference between tocopherol transported into the cells and loss due to catabolism and/or in vitro oxidation). Surprisingly, we also found that the presence of gamma-tocopherol promoted the cellular uptake of alpha-tocopherol. Mass balance considerations suggest that products other than quinone were formed during the incubation of tocopherols with macrophages.ConclusionOur data suggests that gamma-tocopherol could play a significant role in modulating intracellular antioxidant defence mechanisms. Moreover, we found the presence of gamma-tocopherol dramatically influenced the cellular accumulation of alpha-tocopherol, i.e., gamma-tocopherol promoted the accumulation of alpha-tocopherol. If these results could be extrapolated to in vivo conditions they suggest that gamma-tocopherol is selectively taken up by cells and removed from plasma more rapidly than alpha-tocopherol. This could, in part, contribute to the selective maintenance of alpha-tocopherol in plasma compared to gamma-tocopherol.

The influence of dietary iron and tocopherols on oxidative stress and ras-p21 levels in the colon.

The purpose of this investigation was to determine how dietary levels of alpha-tocopherol, gamma-tocopherol and iron influence oxidative stress and ras-p21 levels in the colon. Rats were fed diets deficient in tocopherols (-E) or supplemented with either 0.156 mmol of alpha-tocopherol (AE)/kg diet or 0.156 mmol of gamma-tocopherol (GE)/kg of diet. Half the rats in each of these three groups received dietary iron at a level of 35 mg/kg diet and the other half at eight times this level (280 mg/kg diet). Rats fed the AE diets had higher levels of Vitamin E in feces, colonocytes, plasma and liver than did rats fed the GE diets. Dietary iron levels did not influence tocopherol levels in plasma, liver or feces. For colonocytes, high dietary iron decreased tocopherol levels. The ratio of gamma-tocopherol (in the GE groups) to alpha-tocopherol (in the AE groups) was 0.13 for plasma, 0.11 for liver, 0.28 for colonocytes and 0.51 for feces. The plasma ratio is not, therefore, predictive of the ratio in colonocytes and feces. High levels of dietary iron increased levels of fecal lipid hydroperoxides. Moreover, rats fed the GE diets had lower levels of fecal lipid hydroperoxides than rats fed the AE diets. The levels of ras-p21 were significantly lower in rats fed the GE diets compared with rats fed the AE diets. The gamma-tocopherol may, therefore, play a significant role in preventing colon cancer. High levels of dietary iron were found to promote oxidative stress in feces and colonocytes.