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oxidative stress

Biochemistry: Exposure of cells to pro-oxidant conditions (excessive oxidizing potential) & the cellular response to the stress. The cellular response to oxidative stress is mediated (in part) by genes containing the antioxidant-response element (ARE). The ARE is activated by the transcription factor Nrf2. Mediators of oxidative stress include: 1) superoxide (O2-.), 2) hydrogen peroxide (H2O2) 3) hydroxyl radical (OH.) Excessive production of mediators of oxidative stress or diminished protective mechanisms to remove them may result in: 1) enhanced inflammatory response with secondary tissue damage 2) apoptosis The biochemistry of oxygen & its partial reduction products (O2-., H2O2 & OH.) is not so simple as to allow for simply mopping up this class of 'bad actors'. H2O2 & O2-. are intermediates in enzymatic reactions essential for normal metabolism, including immunological responses. [3,4] The free radical theory on aging [5] & disease [6] has served as a basis of intensive research on oxidative stress since 1956. Pathology: Disorders associated with oxidative stress include: 1) myocardial ischemia & myocardial infarction 2) ischemic stroke 3) Alzheimer's disease 4) Huntington's disease 5) amyotrophic lateral sclerosis 6) Parkinson's disease 7) Tourette syndrome 8) methemoglobinemia 9) pyruvate kinase deficiency 10) glucose-6-phosphate dehydrogenase deficiency

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References

  1. Nguyen T et al, Ann Rev Pharmacol Toxicol 43:233, 2003
  2. UpToDate version 11.3 2003 http://www.uptodate.com
  3. Ball SS. Weindruch R. Walford RL. Antioxidants and the immune response. In: Free Radicals, Aging and Degenerative Disease. Johnson, J.E. (ed.) Modern Aging Research vol. 8, NY: Alan R. Liss pp 427-456, 1986
  4. Nanni E. Sawyer DT. Ball SS. Bruice TC. Redox chemistry of N(5)-ethyl-3-methylflavinium cation and N(5)-ethyl-4a-hydroperoxy-3-methyllumiflavin in dimethyl- formamide; evidence for the formation of the N(5)-ethyl-4a- hydroperoxy-3-methyllumiflavin anion via radical-radical coupling with superoxide ion. J. Am. Chem. Soc. 103:2797, 1981
  5. Harman D, Aging: a theory based on free radical and radiation chemistry, J Gerontol 11:298, 1956
  6. Harman D, Free radical theory of aging: Role of free radicals in the origination and evolution of life, aging and disease processes. In: Johnson JE et al (eds), Free Radicals, Aging and Degenerative Diseases, New York, Liss, 1986