PMID- 17015640 OWN - NLM STAT- MEDLINE DCOM- 20070212 LR - 20171116 IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 320 IP - 1 DP - 2007 Jan TI - Licofelone, a balanced inhibitor of cyclooxygenase and 5-lipoxygenase, reduces inflammation in a rabbit model of atherosclerosis. PG - 108-16 AB - Licofelone, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and cyclooxygenase (COX) 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 with a selective inhibitor of COX-2, rofecoxib. We also assessed the antithrombotic effect of licofelone in rabbit platelet-rich plasma. For this purpose, 30 rabbits underwent injury of femoral arteries, and they were randomized to receive 10 mg/kg/day licofelone or 5 mg/kg/day 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, monocyte chemoattractant protein-1 (MCP-1) gene expression, and the activation of nuclear factor-kappaB 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. Prostaglandin E(2) in rabbit plasma was attenuated by both drugs. Licofelone almost abolished 5-LOX activity by inhibiting leukotriene B4 generation in rabbit neutrophils and prevented platelet thromboxane B2 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. FAU - Vidal, Cristina AU - Vidal C AD - Department of Vascular Research, Fundacion Jimenez Diaz, Autonoma University, Madrid, Spain. cvidal@fjd.es FAU - Gomez-Hernandez, Almudena AU - Gomez-Hernandez A FAU - Sanchez-Galan, Eva AU - Sanchez-Galan E FAU - Gonzalez, Alejandro AU - Gonzalez A FAU - Ortega, Luis AU - Ortega L FAU - Gomez-Gerique, Juan Antonio AU - Gomez-Gerique JA FAU - Tunon, Jose AU - Tunon J FAU - Egido, Jesus AU - Egido J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061002 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Acetates) RN - 0 (Chemokine CCL2) RN - 0 (Cyclooxygenase Inhibitors) RN - 0 (Lipids) RN - 0 (Lipoxygenase Inhibitors) RN - 0 (NF-kappa B) RN - 0 (Pyrroles) RN - 0 (RNA, Messenger) RN - 1HGW4DR56D (Leukotriene B4) RN - 54397-85-2 (Thromboxane B2) RN - K7Q1JQR04M (Dinoprostone) RN - P5T6BYS22Y (licofelone) SB - IM MH - Acetates/*therapeutic use MH - Animals MH - Atherosclerosis/*drug therapy MH - Chemokine CCL2/genetics MH - Cyclooxygenase Inhibitors/*therapeutic use MH - Dinoprostone/blood MH - Disease Models, Animal MH - Leukotriene B4/biosynthesis MH - Lipids/blood MH - *Lipoxygenase Inhibitors/*therapeutic use MH - Macrophages/physiology MH - Male MH - NF-kappa B/antagonists & inhibitors MH - Pyrroles/*therapeutic use MH - RNA, Messenger/analysis MH - Rabbits MH - Thromboxane B2/biosynthesis MH - Tunica Intima/drug effects/pathology EDAT- 2006/10/04 09:00 MHDA- 2007/02/13 09:00 CRDT- 2006/10/04 09:00 PHST- 2006/10/04 09:00 [pubmed] PHST- 2007/02/13 09:00 [medline] PHST- 2006/10/04 09:00 [entrez] AID - jpet.106.110361 [pii] AID - 10.1124/jpet.106.110361 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2007 Jan;320(1):108-16. doi: 10.1124/jpet.106.110361. Epub 2006 Oct 2.