Increased Production of Free Radicals

Helicobacter pylori is associated with chronic gastritis, peptic ulceration and possibly involved in the pathogenesis of gastric carcinoma (Correa and Ruiz, 1992 Dixon, 

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Biological Antioxidant Models. Tea extracts, tea polyphenol fractions, and purified catechins have all been shown to be effective antioxidants in biologically-based model systems. A balance between oxidants and antioxidants is critical for maintenance of homeostasis. Imbalances between free radicals and antioxidants may be caused by an increased production of free radicals or decreased effectiveness of the antioxidants within the reaction system. These imbalances can be caused by the radicals overwhelming the antioxidants within the system, or by an excess of antioxidants leading to a prooxidant functionaHty (105—118). When antioxidant defense systems are consistently overwhelmed by oxidative reactions, significant damage can... 

Direct evidence of increased production of free radicals... 

There is some support for a role for free radicals in the pathogenesis of ischaemic colitis from animal studies. Murthy and Qi (1992) used a spin trap to demonstrate increased production of free radicals up to 60 min after reperfusion, whereas Douglas etal. (1989) demonstrated increases in malondialdehyde and conjugated dienes (presumptive measures of lipid peroxidation) in a rat model of ischaemic colitis. There is no data relating to human ischaemic colitis. 

Direct Evidence of Increased Production of Free Radicals... 

The main dose-limiting toxicity of all anthracyclines is myelosuppression, with neutropenia more commonly observed than thrombocytopenia. In some cases, mucositis is dose-limiting. Two forms of cardiotoxicity are observed. The acute form occurs within the first 2-3 days and presents as arrhythmias or conduction abnormalities, other electrocardiographic changes, pericarditis, and myocarditis. This form is usually transient and is asymptomatic in most cases. The chronic form results in a dose-dependent, dilated cardiomyopathy associated with heart failure. The chronic cardiac toxicity appears to result from increased production of free radicals within the myocardium. This effect is rarely seen at total doxorubicin dosages below 500-550 mg/m2. Use of lower weekly doses or continuous infusions of doxorubicin appear to reduce the incidence of cardiac toxicity. In addition, treatment with the iron-chelating agent dexrazoxane (ICRF-187) is currently approved to prevent or reduce anthracycline-induced cardiotoxicity in women with metastatic breast cancer who have received a total cumulative dose of doxorubicin of 300 mg/m2. All anthracyclines can produce "radiation recall reaction," with erythema and desquamation of the skin observed at sites of prior radiation therapy. 

Increased production of free radicals making possible the induction of enhanced polymerization reactions and treatments... 

ALS because SODl encodes for an antioxidant enzyme. Although the relevance of oxidative stress is not fully understood, it is believed that mutations in SODl promote a structural change that allows a higher rate of interaction between the substrates and the active site of the enzyme, resulting in increased production of free radical species. However, there are not sufficient experimental data supporting this hypothesis because if SODl mutants cause peroxynitrite-dependent cell death in vitro, it would be expected that reduction in the levels of peroxynitrite by inhibition of neuronal nitric oxide synthase (nNOS) would improve the motor neuron outcomes. However, these experiments did not show a decrease in motor neuron damage (Facchinetti et ah, 1999 Upton-Rice et ah, 1999 Son et ah, 2001). 

Both in MCI and AD patients, mean plasma levels of nonenzymatic antioxidants and activity of antioxidant enzymes appeared to be lower than in controls, with no parallel induction of antioxidant enzymes (Keller et al., 2005). In order to explain these results it has been suggested that the increased free radical production in MCI might lead to a rapid consumption of plasma antioxidants without a simultaneous activation of new molecules of antioxidant enzymes. Individuals with MCI, and subsequently with AD, are likely to have an inadequate antioxidant enzymatic activity, unable to counteract the increased production of free radicals during the pathogenesis of the disease. 

Acceleration of chemical reactions due to the increased production of free radicals. An example is the chemiluminometric determination of hydrogen peroxide in lake, rain, tap and purified waters [147]. The reactions involved in the sample preparation step and in the chemiluminometric detection step were accelerated by ultrasound. 

Chemotherapy is a common method of treatment for many types of cancer. The side effects of chemotherapy come about in part because cancer cells are not the only dividing cells in the body. Chemotherapeutic agents cause increased production of free radicals that can be harmful for normal cells, and these free radicals can be bound by antioxidant vitamins and supplements, including lycopene. A large number of studies have reported the beneficial effects of a variety of antioxidants in antineoplastic agents-induced nephrotoxicity, hepatotoxicity, ototoxicity, and peripheral neuropathy [218, 219]. Chemoprotective activities of lycopene [219, 220], and other dietary components that scavenge free radicals induced by exposure to antineoplastic agents [218, 220] have been well documented (Table 129.2). 

Plant phenolics are cmisidered to have a key role as defense compounds when environmental stresses, such as high light, low temperatures, pathogen infection, herbivores, and nutrient dehciency, can lead to an increased production of free radicals and other oxidative species in plants. Both biotic and abiotic stresses stimulate carbon fluxes from the primary to the secondary metabolic pathways. 

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