Hypochlorous acid , neutrophil

Dallegri, F., Ottonello, L., Ballestrero, F., Ferrando, F. and Patrone, F. (1990). Cytoprotection against neutrophil derived hypochlorous acid a potential mechanism for the therapeutic action of 5-aminosalisylic acid in ulcerative colitis. Gut 31, 184-186. 

Sommerburg, O. et al. (2003). Beta-carotene cleavage products after oxidation mediated by hypochlorous acid-A model for neutrophil-derived degradation. Free Rad. Biol. Med. 35( 11) 1480-1490. 

In neutrophils the presence of myeloperoxidase, MPO, within the granules will catalyse the formation of hypochlorous acid from the reaction between hydrogen peroxide and chloride ions while eosinophils MPO preferentially use Br- ions. 

Iron can react with hypochlorous acid, (in neutrophils) to generate the hydroxyl radical ... 

Another amino acid taurine (Figure 29.21) is an effective scavenger of hypochlorous acid, which is known to participate in tissue damage associated with reperfusion injury mediated by neutrophils. Thus, taurine protected against the cytotoxic action of HOC1 in neuronal cells... 

Miyamoto, G., Zahid, N., and Uetrecht, J.P., Oxidation of diclofenac to reactive intermediates by neutrophils, myeloperoxidase, and hypochlorous acid, Chem. Res. Toxicol.,10, 414, 1997. 

Ju, C. and Uetrecht, J.P. 1998. Oxidation of ametabolite of indomethacin (desmethyldeschlorobenzoyl indomethacin) to reactive intermediates by activated neutrophils, hypochlorous acid, and the myeloperoxidase system. Drug Metab. Dispos. 26 676. 

For example, it has been suggested that the adverse reactions caused by a number of drugs such as isoniazid, procainamide, hydralazine could be due to metabolic activation by myeloperoxidase in neutrophils. Thus neutrophils will metabolize procainamide (Fig. 4.38) to a hydroxylamine metabolite. In the presence of chloride ion, myeloperoxidase will produce hypochlorous acid, a strong oxidizing agent, which may be responsible for metabolic activation and toxicity. One of the products is N-chloroprocainamide (see also sect. "Hydralazine," chap. 7). 

Hypochlorous acid generated by neutrophils in the oxidative burst is detoxified by the amino acid taurine, which combines with it to produce taurochloramine. 

Masuda M, Suzuki T, Friesen MD, Ravanat J-L, Cadet J, Pignatelli B, Nishino H, Ohshima H (2001) Chlorination of Guanosine and Other Nucleosides by Hypochlorous Acid and Myeloperoxidase of Activated Human Neutrophils. J Biol Chem 276 40486... 

Candeias LP, Patel KB, Stratford MRL, Wardman P (1993) Free hydroxyl radicals are formed on reaction between the neutrophil-derived species superoxide anion and hypochlorous acid. FEBS Lett 333 151-153... 

M. Masuda et al., Chlorination of guanosine and other nucleosides by hypochlorous acid and myeloperoxidase of activated human neutrophils. J. Biol. Chem. 276, 40486-40496 (2001)... 

D2. Dallegri, F., Goretti, R., Ballestrero, A., Ottonello, L., and Patrone, F., Neutrophil-induced depletion of adenosine triphosphate in target cells Evidence for a hypochlorous acid-mediated process. J. Lab. Clin. Med. 112, 765-772 (1988). 

K24. Kowanko, I. C., Bates, E. J., and Ferrante, A., Mechanisms of human neutrophil-mediated cartilage damage in vitro The role of lysosomal enzymes, hydrogen peroxide and hypochlorous acid. Immunol. Cell Biol. 67,321—329 (1989). 

The relative importance of the contribution of superoxide/hydrogen peroxide and hypochlorous acid in the bacterial killing mechanism is seen in patients with chronic granulomatous disease (CGD, with a defective NADPH-oxidase system), and those that are myeloperoxidase-deficient. CGD patients show persistent multiple infections especially in the skin, lungs, liver and bones by those bacterial strains whose killing by neutrophils requires oxygen. Individuals who are deficient in myeloperoxidase show no symptoms. 

The existence of proteins such as Superoxide Dismutase and Catalase in aerobes often is cited in support of the conclusion that 02 - and HOOH are biological toxins. The present understanding of the biological utilization of hydrogen peroxide includes enzyme-facilitated processes that involve its disproportionation, the dehydrogenation of organic molecules, and the production of hypochlorous acid in neutrophils (equations 23-25). 

Given that the myeloperoxidase enzyme see Peroxidases) within the neutrophils produces hypochlorous acid, an intriguing possibility is that it may combine with another hydrogen peroxide molecule. Such a reaction in the laboratory produces a stoichiometric quantity of singlet dioxygen ( O2), which is selectively reactive with conjugated polyenes. 

The common denominator among the different chronic diseases that are hypothesized to be ameliorated by polyphenol intakes is oxidative stress. Polyphenols are believed to have antioxidant activity both in plants and in those that consume them. Tissue oxidants are produced by inflammatory cells. The first oxidant is superoxide anion radical (O2 ), generated by NADPH oxidase. This free radical is converted to hydrogen peroxide by superoxide dismutase. In activated neutrophils, hydrogen peroxide and chloride are converted to hypochlorous acid (HOCl) by the enzyme myeloperoxidase. ... 

Oxidation of deferiprone with hypochlorous acid, the major oxidant of neutrophil leukocytes, results in the formation of a chemically reactive species, consistent with the quinone metabolite of deferiprone. Deferiprone-related agranulocytosis presumably results from a T cell-mediated immunological reaction, induced by a reactive metabolite of deferiprone (18). In one case agranulocytosis and systemic vasculitis (with arthritis, palpable purpura of the legs, erythema of the palms and soles, and desquamation of the skin over the distal phalanges) occurred in association with deferiprone (22). 

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