Free radical diseases associated with

The European Journal of Nutrition links aging and age-related disorders to acid-alkaline imbalances.1 In my book The Brain Wash, I discuss the dangers of exposure to heavy metals and pesticides, as well as the damage caused by alcohol consumption. These substances contribute to excess acidity in the body as our systems try to metabolize, neutralize, or eliminate them. Once they are in our bodies, it can be difficult to get rid of them. They promote inflammation and increase the formation of free radicals (charged molecules that attack healthy tissues). Both inflammation and free radicals are associated with brain diseases such as Alzheimer s. 

MF effects on FA relatives and healthy donors. (Fanconi anemia is an autosomal recessive disease associated with the overproduction of free radicals, Chapter 31.) It has been shown earlier [215] that FA leukocytes produce the enhanced amount of hydroxyl or hydroxyl-like free radicals, which are probably formed by the Fenton reaction. It was suggested that MF would be able to accelerate hydroxyl radical production by FA leukocytes. Indeed, we found that MF significantly enhanced luminol-amplified CL produced by non-stimulated and PMA-stimulated FA leukocytes but did not affect at all oxygen radical production by leukocytes from FA relatives and healthy donors (Table 21.3). It is interesting that MF did not also affect the calcium ionophore A23187-stimulated CL by FA leukocytes, indicating the absence of the calcium-mediated mechanism of MF activity, at least for FA leukocytes. 

The application of flavonoids for the treatment of various diseases associated with free radical overproduction is considered in Chapter 29. However, it seems useful to discuss here some studies describing the activity of flavonoids under certain pathophysiological conditions. Oral pretreatment with rutin of rats, in which gastric lesions were induced by the administration of 100% ethanol, resulted in the reduction of the area of gastric lesions [157]. Rutin was found to be an effective inhibitor of TBAR products in the gastric mucosa induced by 50%i ethanol [158]. Rutin and quercetin were active in the reduction of azoxymethanol-induced colonic neoplasma and focal area of dysplasia in the mice [159], Chemopreventive effects of quercetin and rutin were also shown in normal and azoxymethane-treated mouse colon [160]. Flavonoids exhibited radioprotective effect on 7-ray irradiated mice [161], which was correlated with their antioxidative activity. Dietary flavones and flavonols protected against the toxicity of the environmental contaminant dioxin [162], Rutin inhibited ovariectomy-induced osteopenia in rats [163],... 

There is suspicion that aluminum is involved in several neurological diseases associated with aging and there is evidence the potential of iron for enhancing free radical generation in nervous tissue is enhanced by aluminum. It is hoped the results of this project will so reveal. 

Recent research has focussed on the role of antioxidant nutrients in reducing the risk of developing coronary heart disease and cancer, the major killers in Western industrialised society. Several epidemiological studies have reported in particular the relevance of a-tocopherol in the context of coronary heart disease and 3-carotene in cancer, especially that of the lung. The development of antioxidant drugs for the treatment of diseases associated with free radicals is a vibrant area of research but depends on the understanding of the mechanisms... 

Antioxidants Combined application of the antioxidants zinc, selenium and tocopherol yielded better treatment results and a reduced mortality rate in alcoholic hepatitis. (75, 139) Alcohol-induced liver diseases are considered to be diseases associated with free radicals oxidative stress is thought to be a contributory factor of disease. (51, 145)... 

Diseases Associated with Free Radicals and Advanced Glycation End Products... 

Atherosclerosis, cancer and degenerative brain diseases may result from specific processes in an organ or a cell system and at the same time may be the result of the universal aging process. Damage to DNA by radicals may be a significant contributor to the age-dependent development of cancer (Halliwell, 1994). Diseases associated with oxidative stress, free radicals and metabolites generating free radicals in the body are listed in Table 3.7 (Stahelin, 1999). It is not yet clear, however, whether the oxidative stress is the primary cause of the diseases or whether formation of radicals is a secondary effect of tissue damage caused by the disease. 

Ageing and the degenerative diseases associated with it are attributed basically to the deleterious side attacks of free radicals on cell constituents and on the connective tissues. The free radicals probably arise largely through reactions involving molecular oxygen catalysed in the cell by oxidative enzymes and in the connective tissues by traces of metals such as iron, cobalt, and manganese. 

Smoking is considered a risk factor for several diseases associated with oxidative stress [180-183]. Cigarette smoke contains NO and NO2, as well as several lipid per-oxy radicals and free radicals [184]. All these components may serve as substrates for oxidation and generate ONOO", likely furthering the cascade of oxidative damage [184,185]. Smokers also have lower amounts of plasma antioxidants, such as ascorbate and vitamin E [186,187] and the consumption of antioxidants attenuate the production of inflammatory mediators [188]. Evidence also suggests that smoking is... 

It has been reported that p-carboUnes and tetrahydro-p-carbolines are potent antioxidants and may be useful for the prevention of diseases associated with oxidative damage [95]. Harmane, harmaline, harmalol, and their peptide conjugates designed and synthesized possess free radical scavenging activity [95, 96]. 

All extracts and their fractions showed HjOj-scavenging ciqiacity in a concentration-dependentmaimer. The values were lower for lOOppmasconqiared to those for 200 ppm level of extracts. The scavei ing of HjOj by extracts and their fractions is attributed to dieir phenolics udiich could donate electrons to HjOj, thus neutralizing it to water. The efficacy of the fractions of each extract was dependent on die chemical nature of phenolic conqiounds involved. Hius, crude extracts, their fractions or purified conqxHinds thereof may be incorporated into foods to minimize free radical-mediated l id peroxidation. They may also be used as alternative drugs/supplements to treat human diseases associated with free radical-mediated tissue damage. 

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