Inhibition of lipoxygenases and cyclooxygenases by linoleyl hydroxamic acid: Comparative in vitro studies

17Citations
Citations of this article
58Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

In this first comparative in vitro study, linoleyl hydroxamic acid (LHA), a simple and stable derivative of linoleic acid, was tested as an inhibitor of several enzymes involved in arachidonic acid metabolism in mammals. The tested enzymes were human recombinant 5-lipoxygenase (h5-LO), porcine leukocyte 12-LO, rabbit reticulocyte 15-LO, ovine cyclooxygenases 1/2 (COX1/COX2), and human microsomal prostaglandin E synthase-1 (mPGES-1). Potato tuber and soybean lipoxygenases (ptLOX and sLOX, respectively) were studied for comparative purposes. LHA inhibited most of the tested enzymes with the exception of mPGES-1. The LHA inhibitory activity increased as follows: mPGES-1 (no inhibition)≪COX1 = COX2 <12-LO≪15-LO. The IC50 values for COX1/COX2, h5-LO, 12-LO, and 15-LO were 60, 7, 0.6, and 0.02 μM, respectively. sLOX was the only tested enzyme that was capable of aerobic oxygenation of LHA, producing 13-hydroperoxy-LHA. The enzyme rapidly inactivated during the reaction. Therefore, LHA could be used as an effective LO/LOX inhibitor without affecting COX1/COX2 and mPGES-1. Possible implications of this observation include treating diseases and pathological states that are caused by (or lead to) hyperproduction of LO-derived metabolites, e.g., inflammation, cardiovascular disorders, cancer, asthma, allergies, psoriasis, and stroke. Copyright © 2008 by the American Society for Biochemistry and Molecular Biology, Inc.

Cite

CITATION STYLE

APA

Butovich, I. A., & Lukyanova, S. M. (2008). Inhibition of lipoxygenases and cyclooxygenases by linoleyl hydroxamic acid: Comparative in vitro studies. Journal of Lipid Research, 49(6), 1284–1294. https://doi.org/10.1194/jlr.M700602-JLR200

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free