Oxygen metabolites

Nifurtimox, a nitrofuran, is a prodrug that is reduced to unstable nitroanion radicals, which react to produce highly toxic oxygen metabolites, such as superoxide and peroxide. Oxidative stress subsequently kills the parasite, which seems to lack effective enzymatic pathways to detoxify oxygen metabolites. 

Any of the collection of oxygenated metabolites of arachidonic acid that are the product of cyclooxygenase, cytochrome P450, or lipoxygenase pathways. 

Sun, F.F., Taylor, B.M. and Fleming, W.E. (1993). Formation of intracellular reactive oxygen metabolites during irreversible cell injury. FASEB J. 7, A658. 

Andrews, F.J., Malcontent , C. and O Brien, P.E. (1992). Sequence of gastric mucosal injury foUowing ischaemia and reperfusion the role of reactive oxygen metabolites. Dig. Dis. Sci. 37, 1356-1361. 

Davies, G.K, Simmonds, N.J., Stevens, T.R.J., Grandison, A., Revell, P., Blake, D.R. and Rampton, D.S. (1992a). Mucosal reactive oxygen metabolite production in duodenal ulcer disease. Gut 33, 1467-1472. 

Harris, M.L., Schiller, H.J., Reilly, P.M., Donowitz, M., Grisham, M.B. and Bulkley, G.B. (1992). Free radicals and other reactive oxygen metabolites in inflammatory bowel disease cause, consequence or epiphenomenon Pharmac. Ther. 53, 375-408. 

Haydek, J., Parveen, S., List, T., Doria, M. and Keshvarian, A. (1991). Reactive oxygen metabolites in experimental colitis the effect of catalase. Gastroenterology, 100, A585. 

Hiraishi, H., Terano, A., Ota, S., Ivey, K.J. and Sugjmoto, T. (1987). Oxygen metabolite-induced cytotoxicity to cultured rat gastric mucosal cells. Am. J. Physiol. 253, G40-G48. 

Hiraishi, H., Razandi, M., Terano, A. and Ivey, K.J. (1990). Antioxidant defenses of culture gastric mucosal cells against toxic oxygen metabolites. Role of glutathione redox cycle and endogenous catalase. Gastroenterology 98, A544. 

Keshavarzian, A., Doria, M.I., Sedghi, S., Kanofeky, J.R., Hecht, D., Holmes, E.W., Ibrahim, C., List, T., Urban, G., Gaginella, T. and Fields, J.Z. (1992a). Mitomycin C-induced colitis in rats a new animal model of acute colonic inflammation implicating reactive oxygen metabolites. J. Lab. Clin. Med. 120, 778-791. 

Keshavarzian, A., Zapeda, D., List, T. and Mobarhan, S. (1992d). High levels of reactive oxygen metabolites in colon cancer tissues analysis by chemiluminescence probe. Nutr. Cancer 17, 243-249. 

Rozga, J. (1989). The role of reactive oxygen metabolites in the pathogenesis of ulcerative colitis a speculative synthesis. Materia Med. Pol. 21, 263-268. 

Verspaget, H.W., Mulder, T.P.J., Van der Sluys Veer, A., Pena, A.S. and Earners, C.B.H.W. (1991). Reactive oxygen metabolites and colitis a disturbed balance between damage and protection. A selective review. Scand. J. Gastroenterol. 26 Suppl. 188, 44-51. 

Williams, J.G. (1990). Phagoeyftes, toxic oxygen metabolites and inflammatory bowel disease, implications for treatment. Ann. R, Coll. Sutg. Engl. 72, 253-262. 

Williams, J.G. and Hallett, M.B. (1989).Effect of sulphasalazine and its active metabolite, 5-aminosalicylic acid, on toxic oxygen metabolite production by neutrophils. Gut 30, 1581-1587. 

In addition to the well-characterized role of iron in catalysing redox interactions, other metallic contaminants, for example, nickel, may also contribute. In vivo toxicity studies have demonstrated the capacity of nickel particulate compounds to induce tumours following intraperitoneal injection (Pott etal., 1987). Such activity is proportional to their phagocytic uptake, and to the associated respiratory burst and generation of PMN-derived reactive oxygen metabolites (ROMs), a proposed pathogenic mechanism (Evans et al., 1992a). 

Goodlick, L.A. and Kane, A.B. (1986). Role of reactive oxygen metabolites in crocidolite asbestos toxicity to mouse macrophages. Cancer Res. 46, 5558-5566. 

Yano, E., Urano, N. and Evans, P.H. (1991). Reactive oxygen metabolite production induced by mineral fibres. In Mechanisms in Fibre Carcinogenesis (eds. R.C. Brown, J.A. Hoskins and N.F. Johnson) pp. 433-438. Plenum, New York. 

In a study looking at oxygenated metabolites of AEA and their interaction with the cannabinoid system, a series of hydroxylated alkyl chains was prepared using different lipoxygenases as biocatalysts [152-154]. Of the seven AEA derivatives prepared, only the 5R-hydroxy (208), 125 -hydroxy (209) and 155 -hydroxy (210) derivatives had any affinity for the CBi receptor. Interestingly, the IdV-hydroxy compound (211) that was inactive at the CBi receptor displayed some affinity for the CB2 receptor [152] (see Table 6.18). 

Manna, C. et al. (1997). The protective effect of the olive oil polyphenol (3,4-dihydroxyphenyl)-ethanol counteracts reactive oxygen metabolite-induced cytotoxicity in Caco-2 cells. J. Nutr. 127(2) 286-292. 

Schreiber s model has also proved to be a general approach to a series of oxygenated metabolites of arachidonic acid, such as lipoxin A and lipoxin B.50 The family of linear oxygenated metabolites of arachidonic acid has been implicated in immediate hypersensitivity reactions, inflammation, and a number of other health problems. Among these metabolites, several compounds, such as lipoxin A, lipoxin B, 5,6-diHETE, and 14,15-diHETE possess 1-substituted (/ )-1 -alken-3.4-diol 84 as a common substructural moiety. Therefore, the car-binol 83 is an ideal substrate for generating compound 84 by applying Sharpless epoxidation reaction.50... 

Low levels of mercuric chloride in polymorphonuclear cells may profoundly alter the cell respiratory burst, measured as chemiluminiscence, oxygen consumption and H2Oz production [171-173], depress phagocytic capacity [172, 173] and enhance release of lysosomal enzymes [ 172] with minimal loss of cell viability. A stimulation of oxygen metabolism in vivo might promote tissue injury, via the local production of free oxygen metabolites, in addition to depression of host defence [173],... 

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