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Antioxidants protect us against us the chronic diseases of old age but it is also important to appreciate that they may have a role in guarding us against the consequences of acute clinical conditions such as heart attacks or strokes. It takes time to load tissues with lipophilic antioxidants. To gain these benefits, we must have the protection in place before the incident. As we age, it becomes more likely that we will experience an acute clinical situation. To learn how antioxidants may prevent the consequences of stroke and heart attack, we must use animal models. The two reports below illustrate how lipoic acid and tocotrienols can protect against ischemia, an interruption to the blood flow to the heart or the brain. Much of the damage to these organs after a stroke or heart attack occurs during the reperfusion phase, when the blood flows back into damaged tissue. In the first example, we fed rats with a diet high in tocotrienols for six weeks and compared the results of a simulated heart attack with control animals fed a normal diet. After 40 minutes of global ischemia the isolated hearts from control animals exhibited a 20-25% recovery in mechanical activity. The hearts from the tocotrienol-fed animals made an almost complete recovery from these injuries. In another model, we studied the protection of the brain against stroke by lipoate. 30 minutes of total ischemia to the brain was established by carotid artery occlusion in the rat. After release of the occlusion and re-establishment of blood flow 80% of the animals died. However, if lipoate was injected immediately prior to removal of occlusion, 80% of the animals lived. Ischemia was accompanied by a drastic loss of glutathione (GSH) in the three different brain regions that were tested. In these regions, there were also elevations in the thiobarbituric acid reactive substances (TBARS), indicating enhanced lipid peroxidation. The loss of glutathione and the increased lipid peroxidation in these three brain regions were almost completely prevented by lipoate administration. In both these studies antioxidant network activity was manifested and the potential of antioxidants to diminish the consequences of heart attacks and strokes demonstrated.T he use of antioxidants as an adjunct to aids therapy has been proposed and some small scale human trials are in progress. In vitro research helps identify promising antioxidant combinations.--
Inflammatory Disorders Cell-adhesion molecule expression is important for leukocyte activation and recruitment. Over-expression of cell-adhesion molecules can lead to inflammatory diseases, like inflammatory bowel diseases and acute respiratory distress syndrome (ARDS). Receptor-mediated activation of NF-kB results downstream in the production of various cell-adhesion molecules such as ICAM 1, ICAM 3, VCAM 1 and ß-selectins. Expression of these cell-adhesion molecules by human cells can be inhibited in a concentration-dependent manner by alpha lipoic acid. Very much lower concentrations of lipoate are needed to inhibit cell-adhesion molecule expression when the combination of vitamin E and lipoate is utilized. At these low concentrations, either vitamin E or lipoate alone are almost without effect. .
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