In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 54, No. 10 ( 2010-02-18), p. 1385-1392
Abstract:
It has been known that reactive oxygen and nitrogen species such as nitric oxide (NO), superoxide radical (.O−2) and their byproduct peroxynitrite (ONOO−) induce cellular and tissue injury, ultimately resulting in several human diseases. In this study, we examined scavenging effects of 3-methyl-1,2-cyclopentanedione (MCP) from coffee extract on the reactivity of those toxic molecules. MCP significantly inhibited both the oxidation of 2,7-dichlorodihydrofluorescein diacetate (H2DCFDA) by reactive oxygen species (ROS) (mainly .O−2) from kidney homogenate (41% at 100 μM) and the generation of fluorescent 4,5-diaminofluorescein (DAF-2) by NO from sodium nitroprusside (IC50 (concn producing 50% inhibition), 63.8 μM). More potently, however, MCP suppressed the oxidation of dihydrorhodamine 123 (DHR 123) to fluorescent rhodamine 123 mediated by authentic ONOO− with an IC50 value of 3.3 μM. The neutralizing effect of the reactivity of ONOO− by MCP was due to electron donation, not nitration of the compound. Additionally, MCP also decreased ONOO− formation of nitrotyrosine adducts of glutathione (GSH) reductase, and consequently protected the enzyme activity of GSH reductase against decreasing by ONOO−, indicating that MCP may prevent ONOO−-induced damage of GSH reductase. Furthermore, MCP only weakly suppressed NO production, which is one of the upstream sources of ONOO− in-vivo, suggesting that NO production may be not a pharmacological target for MCP. Taken together, our results suggest that MCP may be regarded as a selective regulator of ONOO−-mediated diseases via direct scavenging activity of ONOO−.
Type of Medium:
Online Resource
ISSN:
0022-3573
,
2042-7158
DOI:
10.1211/002235702760345473
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2010
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
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