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Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages

Authors :
Luisa Tesoriere
Fulvio D'Acquisto
Alessandro Attanzio
Mario Allegra
M. A. Livrea
Allegra, M
D'Acquisto, F
Tesoriere, L
Attanzio, A
Livrea, MA
Source :
Redox Biology, Redox Biology, Vol 2, Iss C, Pp 892-900 (2014)
Publication Year :
2014
Publisher :
Elsevier BV, 2014.

Abstract

Macrophages come across active prostaglandin (PG) metabolism during inflammation, shunting early production of pro-inflammatory towards anti-inflammatory mediators terminating the process. This work for the first time provides evidence that a phytochemical may modulate the arachidonate (AA) metabolism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, promoting the ultimate formation of anti-inflammatory cyclopentenone 15deoxy-PGJ2. Added 1 h before LPS, indicaxanthin from Opuntia Ficus Indica prevented activation of nuclear factor-κB (NF-κB) and over-expression of PGE2 synthase-1 (mPGES-1), but up-regulated cyclo-oxygenase-2 (COX-2) and PGD2 synthase (H-PGDS), with final production of the anti-inflammatory cyclopentenone. The effects were positively related with concentration between 50 and 100 µM. Indicaxanthin did not have any effect in the absence of LPS. A kinetic study investigating the redox status of LPS-stimulated macrophages between 0.5 and 12 h, either in the absence or in the presence of 50–100 µM indicaxanthin, revealed a differential control of ROS production, with early (0.5–3 h) modest inhibition, followed by a progressive (3–12 h) concentration-dependent enhancement over the level induced by LPS alone. In addition, indicaxanthin caused early (0.5–3 h) concentration-dependent elevation of conjugated diene lipid hydroperoxides, and production of hydroxynonenal-protein adducts, over the amount induced by LPS. In LPS-stimulated macrophages indicaxanthin did not affect PG metabolism when co-incubated with either an inhibitor of NADPH oxidase or vitamin E. It is concluded that LPS-induced pro-oxidant activity of indicaxanthin at the membrane level allows formation of signaling intermediates whose accumulation modulates PG biosynthetic pathway in inflamed macrophages.<br />Graphical abstract<br />Highlights • Phytochemical indicaxanthin promotes synthesis of anti-inflammatory prostaglandins. • Prooxidant activity of indicaxanthin causes anti-inflammatory response in macrophages. • Indicaxanthin modulates the redox status of LPS-stimulated macrophages. • Membrane lipid peroxides are signaling intermediates in inflamed macrophages.

Details

ISSN :
22132317
Volume :
2
Database :
OpenAIRE
Journal :
Redox Biology
Accession number :
edsair.doi.dedup.....8919fc92a33381c83513ef744026b7b5
Full Text :
https://doi.org/10.1016/j.redox.2014.07.004