Characterization of the adaptive response mechanisms in rat liver induced by vitamin E and selenium deficiency
Abstract
We have used a model of dietary deficiency that leads to a chronic oxidative stress to evaluate responses invoked to boost antioxidant cellular defense systems. The present studies demonstrates that there is adaptive response mechanisms invoked in the absence of vitamin E. The central component of this adaptive mechanism is coenzyme Q and its recycling factors. In our first study, Long Evans hooded weaning rats were fed a diet without vitamin E and Se for six weeks, leading the animals to be deficient in both nutrients (−E −Se). Deficiency was accompanied by a two-fold increase in redox activities associated with transplasma membrane electron transport, an increase in ascorbate and glutathione was found in the liver tissue, increased microsomal, glucose-6-phosphate dehydrogenase and an increase of cytosolic Ca2+-independent phospholipase A2. Liver plasma membranes isolated from these rats were more sensitive to lipid peroxidation, although they contained 40% greater amounts of ubiquinone than the plasma membranes from rats consuming control diets (+E +Se). The incubation of plasma membranes with NAD(P)H resulted in protection against peroxidation, and this effect was more pronounced in −E −Se membranes. In our second study, Long Evans hooded rats were fed a diet without vitamin E. The oxidative stress induced here led to invocation of a sequence of antioxidant defense mechanisms in the liver of vitamin E-deficient animals. This single nutrient deficiency allowed us to characterize a three-phase adaptive response to oxidative stress induced by vitamin E deficiency. Phase one occurred when tocopherol was depleted from membranes and involved increased concentrations and capacity of primary antioxidants, ascorbate and ubiquinol and their recycling enzymatic machinery. The early changes appear to be sufficient to preserve the balance between ROS and defense mechanisms as the rats continued to grow as well as the control during this time period. Phase two was characterized by the onset of oxidative stress and increased activity of radical scavenging antioxidant systems. Phase three was characterized by accumulating concentrations of the product of oxidative stress damage along with the induction of lipid metabolizing enzyme systems.
Degree
Ph.D.
Advisors
Burgess, Purdue University.
Subject Area
Nutrition
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