Received for publication July 5, 2006.
Revised September 29, 2006.
Accepted for publication September 29, 2006.

LICOFELONE, A BALANCED INHIBITOR OF CYCLOOXYGENASE AND 5-LIPOXYGENASE, REDUCES INFLAMMATION IN A RABBIT MODEL OF ATHEROSCLEROSIS

Abstract

Licofelone, a dual anti-inflammatory drug, which inhibits 5-lipoxygenase and cyclooxygenase enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade mediated antithrombotic effect and a better gastrointestinal tolerability. We examined the anti-inflammatory effect of licofelone on atherosclerotic lesions as well as in isolated neutrophils from whole blood of rabbits compared to a selective inhibitor of COX-2, rofecoxib. We also assessed the antithrombotic effect of licofelone in rabbit platelet-rich plasma. For this purpose, thirty rabbits underwent injury of femoral arteries and were randomized to receive 10 mg/kg/day of licofelone or 5 mg/kg/day of rofecoxib or no treatment during 4 weeks with atherogenic diet in all cases. Ten healthy rabbits were used as controls. Neutrophils and platelets were isolated from peripheral blood of rabbits for ex vivo studies. Licofelone reduced intima/media ratio in injured arteries, the macrophages infiltration in the neointimal area, MCP-1 gene expression and the activation of NF-B in rabbit atheroma. Moreover, licofelone inhibited COX-2 and 5-LOX protein expression in vascular lesions. Rofecoxib only diminished COX-2 protein expression and MCP-1 gene expression in vascular atheroma. PGE₂ in rabbit plasma was attenuated by both drugs. Licofelone almost abolished 5-LOX activity by inhibiting LTB4 generation in rabbit neutrophils and prevented platelet TXB₂ production from whole blood. Licofelone reduces neointimal formation and inflammation in an atherosclerotic rabbit model more markedly than rofecoxib. This effect, together with the antiplatelet activity of licofelone, suggests that this drug may have a favorable cardiovascular profile.

Key words: 5-lipoxygenase, Atherosclerosis, Cyclooxygenase 1, Cyclooxygenase 2, Eicosanoids, Inflammation

This article has been cited by other articles:

				A. Koeberle, U. Siemoneit, U. Buhring, H. Northoff, S. Laufer, W. Albrecht, and O. Werz Licofelone Suppresses Prostaglandin E2 Formation by Interference with the Inducible Microsomal Prostaglandin E2 Synthase-1 J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 975 - 982. [Abstract] [Full Text] [PDF]

				R. Horrillo, A. Planaguma, A. Gonzalez-Periz, N. Ferre, E. Titos, R. Miquel, M. Lopez-Parra, J. L. Masferrer, V. Arroyo, and J. Claria Comparative Protection against Liver Inflammation and Fibrosis by a Selective Cyclooxygenase-2 Inhibitor and a Nonredox-Type 5-Lipoxygenase Inhibitor J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 778 - 786. [Abstract] [Full Text] [PDF]