Effect of ibuprofen on the development of fat-induced atherosclerosis in New Zealand rabbits

Abstract

Inflammatory mechanism plays important role in the pathogenesis of atherosclerosis. The migration of monocytes to activated arterial endothelium with involvement of chemokines and adhesion molecules is one of the earliest detectable events in it. The monocyte chemotactic protein type 1 (MCP-1) is known for its potent attractant action on monocytes, precursors of foam cells accounting for the bulk of atheromatous plaques. MCP-1 is synthesized in vivo by activated endothelial cells expressing the MCP-1 gene under control of transcription factor-κB (NF-κB). Inhibitors of NF-κB activation include ibuprofen (2-[4-isobutyl-phenyl]-propionic acid) belonging to non-steroid anti-inflammatory drugs (NSAIDs). The aim of this study was to determinate the effect of ibuprofen on the development of fat-induced atherosclerosis in New Zealand White rabbits.

Ibuprofen significantly reduced the expression of the MCP-1 gene both in rabbit groups fed the standard chow for 2 and 3 months as compared with control groups consumed the standard chow without ibuprofen for 2 (p<0.005) and 3 months (p<0.01), respectively, and with control groups consumed high-cholesterol chow for 2 (p<0.005) and 3 (p<0.05) months, respectively. Ibuprofen significantly reduced the expression of the MCP-1 gene in the study group fed the high-cholesterol chow for 2 months as compared with the group consumed the high-cholesterol chow without ibuprofen for 2 months (p<0.01). Nevertheless, ibuprofen failed to protect against outcomes of the high-fat diet such as atherosclerotic lesions of the aorta, elevated concentrations of cholesterol and triglycerides, and markedly higher liver/body mass and adrenals/body mass ratios. It was concluded that low doses of ibuprofen suppress the expression of the MCP-1 gene without any effect on the progress of fat-induced atherosclerosis.