Abstract
Monosodium urate crystals are a naturally occurring pro-inflammatory agent associated with the manifestations of the rheumatic disorder, gout. This disease is characterized by occasional periods of severe pain and inflammatory swelling that, if untreated, resolves spontaneously within a few days1. Although urate crystals are known to be the etiologic agent for gout, and their accumulation seems to be the major pathophysiological event leading to inflammatory episodes, additional factors influence the inflammatory response. Urate crystal deposition in joints may occur without associated inflammation2 and inflammatory attacks may remit although urate crystals are still present in the joints3. Prostaglandins (PGs) appear to play a prominent role in the onset of gout attacks because non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit PG formation, are considered the drugs of choice for the treatment of acute attacks4. Using a mouse model of urate crystal-induced peritonitis, we have found that while urate crystals triggered an initial burst of eicosanoid products, at later times additional arachidonic acid metabolism was attenuated in a fashion independent of substrate concentration5. The present study further investigate this phenomena and demonstrate that urate crystal administration resulted in five fold elevation of the intracellular and extracellular pools of reduced glutathione (GSH) and that the elevated GSH attenuated PG formation by shifting the cyclooxygenase (COX) products profile from PG to 12-hydroxyheptadecatrienoic acid (12-HHT).
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Margalit, A., Hauser, S.D., Isakson, P.C. (1999). Regulation of in Vivo Prostaglandin Biosynthesis by Glutathione. In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E.A. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4. Advances in Experimental Medicine and Biology, vol 469. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4793-8_25
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DOI: https://doi.org/10.1007/978-1-4615-4793-8_25
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