Antioxidant tissue levels

Another method of increasing antioxidant tissue levels is facilitated by using liposomes. Liposomal dmg delivery is advantageous to using the oral route in that there is a multiplicity of possible administration routes. They can be used topically, orally (using the gastrointestinal tract), or delivered by aerosol to the lung. 

The DNA adducts, deoxyadenosine and deoxygua-nosine, which are induced by malondialdehyde, the end-product of lipid peroxidation, accumulate in human breast tissues. These adducts are present at relatively higher concentrations in breast cancer cells compared to normal breast cells. In a recent study, serum antioxidative vitamin levels and lipid peroxidation were compared in gastric cancer patients. The level of serum ascorbic acid, a-tocopherol, p-carotene, and retinol were assessed. The levels of ascorbic acid in patients with gastric carcinoma were less than one-fifth of that in the control group, and the production of p-carotene and a-tocopherol were decreased, as well. 

ROS and NO appears to play a critical role in this phenomenon.In support, microvascular ROS levels (as assessed using oxidant-sensitive fluorescent probes) increased during hypoxia. Antioxidants attenuated the hypoxia-induced increase in ROS formation, leukocyte adherence, vascular permeability, and leukocyte emigration. Interventions designed to increase tissue levels of NO also attenuated these microvascular inflammatory responses during hypoxia. ... 

The detection and quantification of one or more of the above lipid peroxidation produas (primary and/or secondary) in appropriate biofluids and tissue samples serves to provide indices of lipid peroxidation both in ntro and in vivo. However, it must be stressed that it is absolutely essential to ensure that the products monitored do not arise artifactually, a very difiScult task since parameters such as the availability of catalytic trace metal ions and O2, temperature and exposure to light are all capable of promoting the oxidative deterioration of PUFAs. Indeed, one sensible precaution involves the treatment of samples for analysis with sufficient levels of a chainbreaking antioxidant [for example, butylated hydroxy-toluene (BHT)] immediately after collection to retard or prevent peroxidation occurring during periods of storage or preparation. 

The importance of vitamin E for maintenance of lipid integrity in vivo is emphasized by the fact that it is the only major lipid-soluble chain-breaking antioxidant found within plasma, red cells and tissue cells. Esterbauer etal. (1991) have shown that the oxidation resistance of LDL increases proportionately with a-tocopherol concentration. In patients with RA, synovial fluid concentrations of a-tocopherol are significantly lower relative to paired serum samples (Fairburn et al., 1992). The low level of vitamin E within the inflamed joint implies it is being consumed via its role in terminating lipid peroxidation and this will be discussed further in Section 3.3. 

Ascorbic acid (vitamin C) depletion is the most consistent evidence of compromised antioxidant status in diabetes with reports of reduced levels and altered metabolic turnover in several tissues in experimentally induced diabetes in animals (Rikans, 1981 Yew, 1983 McLennan et al., 1988) and in patients with diabetes (Som et al., 1981 Jennings et al., 1987 Sinclair et al., 1991). 

A more recent study, which measured three established markers of free-radical activity in addition to serum ascorbic acid in two groups of elderly diabetic patients (with and without retinopathy), found no significant differences in any of the markers between patients and age-matched controls despite significant depletion of ascorbic acid in patients with diabetes, especially those with retinopathy (Sinclair et al., 1992). These rather paradoxical findings suggest the existence of a complex interrelationship between the levels of individual antioxidant molecules in cells and tissues. 

Other considerations such as demonstrating a direct correlation between the level of oxidative stress and tissue damage in diabetes and showing that antioxidant therapy leads to prevention, arrest or regression of diabetic complications are also important and must be the basis of future well-designed studies. 

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