Jump to main content
Jump to site search

Issue 5, 2012
Previous Article Next Article

Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network

Author affiliations

Abstract

The arachidonic acid (AA) metabolic network produces key inflammatory mediators which have been considered as hallmark contributors in various inflammatory related diseases. Enzymes in this network, such as 5-lipoxygenase (5-LOX), cyclooxygenase (COX), leukotriene A4 hydrolase (LTA4H) and prostaglandin E synthase (PGES), have been used as targets for anti-inflammatory drug discovery. Multi-target drugs and drug combinations have also been developed for this network. However, how the inhibitors alter the dynamics of metabolite production and which combinatorial target intervention solutions are better needs further exploration. We did a system based intervention analysis on the AA metabolic network. Using an LC-MS/MS method, we quantitatively studied the eicosanoid metabolites responses of AA metabolic network during stimulation of Sprague Dawley rat blood samples with the calcium ionophore. Our results indicate that inhibiting the upstream rather than the downstream target of 5-LOX pathway will simultaneously alter the AA metabolism to the COX pathway (and vice versa). Therefore, single-target inhibitors cannot control all the inflammatory mediators at the same time. We also suggest that in the case of multiple-target anti-inflammatory solutions, the combination of inhibitors of the downstream enzymes may have stronger inhibition efficiency and cause less side-effects compared to the other solutions. One therapeutic strategy, LTA4H/COX inhibition solution, was found promising for the intervention of inflammatory mediator biosynthesis and at the same time stimulating the production of anti-inflammatory agents.

Graphical abstract: Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network

Back to tab navigation

Supplementary files

Article information


Submitted
17 Dec 2011
Accepted
28 Feb 2012
First published
01 Mar 2012

Mol. BioSyst., 2012,8, 1585-1594
Article type
Paper

Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network

C. He, Y. Wu, Y. Lai, Z. Cai, Y. Liu and L. Lai, Mol. BioSyst., 2012, 8, 1585
DOI: 10.1039/C2MB05503A

Search articles by author

Spotlight

Advertisements