Selective peroxynitrite scavenging activity of 3-methyl-1,2-cyclopentanedione from coffee extract | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

1655426

Reference Type

Journal Article

Title

Selective peroxynitrite scavenging activity of 3-methyl-1,2-cyclopentanedione from coffee extract

Author(s)

Kim, AR; Zou, Y; Kim, HS; Choi, JS; Chang, GY; Kim, YJ; Chung, HY

Year

2002

Is Peer Reviewed?

Yes

Journal

Journal of Pharmacy and Pharmacology
ISSN: 0022-3573

Publisher

ROYAL PHARMACEUTICAL SOC GREAT BRITAIN

Location

LONDON

Volume

Issue

Page Numbers

1385-1392

Language

English

PMID

12396301

DOI

10.1211/002235702760345473

Web of Science Id

WOS:000179150800011

Abstract

It has been known that reactive oxygen and nitrogen species such as nitric oxide (NO), superoxide radical (*O2-) 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 *O2-) from kidney homogenate (41% at 100 microM) and the generation of fluorescent 4,5-diaminofluorescein (DAF-2) by NO from sodium nitroprusside (IC50 (concn producing 50% inhibition), 63.8 microM). 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 microM. 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-.