Oxidant stress and free radicals

While many biological molecules may be targets for oxidant stress and free radicals, it is clear that the cell membrane and its associated proteins may be particularly vulnerable. The ability of the cell to control its intracellular ionic environment as well as its ability to maintain a polarized membrane potential and electrical excitability depends on the activity of ion-translocating proteins such as channels, pumps and exchangers. Either direct or indirect disturbances of the activity of these ion translocators must ultimately underlie reperfiision and oxidant stress-induced arrhythmias in the heart. A number of studies have therefore investigated the effects of free radicals and oxidant stress on cellular electrophysiology and the activity of key membrane-bound ion translocating proteins. 

The authors cited a combination of ischemia and exci-totoxicity due to cocaine exposure as the possible cause of the brain injury. Oxidative stress and free radicals associated with cerebral hypoxia contribute to cell damage and death. 

F. Oxidative Stress and Free Radicals with Classic Examples... 

Oxidative stress and free-radicals The production of free-radicals and other reactive species has been much implicated in cytotoxicity. This topic is discussed in more detail elsewhere see ANTIOXIDANTS PREE-RADICAL SCAVENGERS nitric oxide synthase inhibitors. The production of these species in oxidative stress is well established. Advances in therapy may well be in the direction of boosting and augmenting natural defence processes, for example, by superoxide dismutase (SOD), catalase, a-tocopherol, glutathione, ascorbic acid and perhaps melatonin. Surprisingly, some forms of the enzyme SOD can be administered in vivo and are protective. 

Albano, E. (2006). Alcohol, oxidative stress and free radical damage. Proc. Nutr. Soc. 65, 278-290. 

Lipolal aldol condensation derivatives, (n), prepared by Haj-Yehia (4) were effective as reactive oxygen species scavengers and used in treating conditions associated with oxidative stress or free radical injury including mitochondrial cytopathies and HIV infection. 

Pacific RE, Davies KJA (1991) Protein,lipid, and DNA repair systems in oxidative stress the free radical theory of aging revisited. Gerontology 37 166-180... 

Institute, Lisbon, Portugal) in the August/September 2006 Townsend Letter for Doctors Patients. (Mitochondria are the subcellular organelles that produce cellular energy via the formation of ATP, or adenosine triphosphate.) The article speaks of breaks in the mitochondrial DNA (MTDNA) traceable to oxidative stress from free radicals and possibly to chemotherapy itself, which can lead to cellular defects, mutations, and cancer. The formation and renewal of MTDNA involves the enzyme mitochondrial polymerase (and the inhibition of this enzyme can be viewed as one more factor in this complex scenario). 

Risby T. H. and Sehnert S. S., Clinical application of breath biomarkers of oxidative stress status, Free. Radical. Biol. Med., 27,1182-1192, 1999. 

It may be emphasized again here that the botanical polysaccharides with immunomodulatory properties are also known to be potent antioxidants [5,27]. Many studies have shown that the oxidative stress producing free radicals lead to both initiation and promotion of multistage carcinogenesis [25,35]. These findings suggest that the plant polysaccharides, which are natural antioxidants, immunomodulators as well as antitumor agents, are expected to be the future chemotherapeutics of choice. 

The associations between issues B, C and vitamin B12 are discussed here. Concerning issue A, oxidative stress by free radicals formed during the reducing process of homocysteine is reported to injure endothelial cells directly (Mansoor et al. 1995). 

Price, A. Hendry, G. (1987). The significance of the tocopherols in stress survival in plants. In Free Radicals, Oxidant Stress and Drug Action, ed. C. Rice Evans, pp. 443-50. London Richelieu Press. 

The protective effects of carotenoids against chronic diseases appear to be correlated to their antioxidant capacities. Indeed, oxidative stress and reactive oxygen species (ROS) formation are at the basis of oxidative processes occurring in cardiovascular incidents, cancers, and ocular diseases. Carotenoids are then able to scavenge free radicals such as singlet molecular oxygen ( O2) and peroxyl radicals particularly, and protect cellular systems from oxidation. 

Turner, J.J.O., Rice-Evans, C., Davies, M.J. and Newman, E.S.R. (1991). The formation of free radicals by cardiac myocytes under oxidative stress and the effects of electron-donating drugs. Biochem. J. 277, 833-837. 

Collier et al. (1990) extended their studies relating to oxidative stress and diabetes by demonstrating that the levels of several free-radical scavengers (red cell superoxide dismutase, plasma thiols) were significantly reduced in 22 type 2 diabetic patients (mean age 53 years) in comparison with 15 control subjects (mean age 51 years). No significant diflFerences in red cell lysate thiols or... 

Gilmour, P.S. et al. (1997) Free radical activity of industrial fibers role of iron in oxidative stress and activation of transcription factors. Environmental Health Perspectives, 105, 1313-1317. 

As hydroxyl or hydroxyl-like radicals are produced by the superoxide-driven Fenton reaction, superoxide overproduction must also occur in thalassemic cells. First, it has been shown by Grinberg et al. [382], who demonstrated that thalassemic erythrocytes produced the enhanced amount of superoxide in comparison with normal cells in the presence of prooxidant antimalarial drug primaquine. Later on, it has been found that the production of superoxide and free radical-mediated damage (measured through the MetHb/Hb ratio) was much higher in thalassemic erythrocytes even in the absence of prooxidants, although quinones (menadione, l,4-naphthoquinone-2-methyl-3-sulfonate) and primaquine further increased oxidative stress [383]. Overproduction of superoxide was also observed in thalassemic leukocytes [384]. 

It is known that erythrocytes from patients with sickle cell anemia contain various types of abnormal iron deposits [398], which could be the origin of the overproduction of oxygen radicals in these cells. Indeed, Hebbel et al. [399] has showed that sickle erythrocytes spontaneously generate approximately twice as much superoxide as normal erythrocytes. Later on, it has been shown that these cells are also able to generate hydroxyl radicals catalyzed by three types of iron, preexisting free iron, free iron released during oxidative stress, and iron that cannot be chelated with desferrioxamine [400]. 

Riley, P. A., 1994, Free radicals in biology oxidative stress and the effects of ionizing radiation, Int. J. Radial. Biol. 65 27-33. 

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