Bisphosphonates are antiatherosclerotic, suppress monocyte-macrophages, and modulate proinflammatory mediators. Prostaglandin (PG) E2, thromboxane (TX) A2, and cyclooxygenase-2 (COX-2) enzyme are involved in inflammation and atherosclerosis. We studied the effects of four bisphosphonates (etidronate, clodronate, tiludronate, and alendronate) on PGE2 and TXB2 production in human whole blood and monocytes. PGE2 and TXB2 were determined by direct radioimmunoassay and COX-2 expression by Western blot. In whole blood, the bisphosphonates did not modulate the increase in PGE2 and TXB 2 concentrations induced by calcium ionophore A23187 or lipopolysaccharide (LPS). None of the bisphosphonates did change PGE2 and TXB2 concentration after spontaneous clotting. A23187- and spontaneous clotting-induced PGE2 and TXB2 productions were inhibited over 90% by acetylsalicylic acid (ASA), and LPS-induced PGE 2 and TXB2 formations were inhibited over 90% by nimesulide. None of the bisphosphonates altered these inhibitions. In monocytes, etidronate and clodronate augmented A23187-stimulated PGE2 production 2.5- to 3.2-fold (p < 0.05). LPS- or A2318-induced elevations in TXB2 were not influenced by the bisphosphonates. The tested bisphosphonates neither induced COX-2 expression nor modulated LPS-induced COX-2 expression in monocytes. The results suggest that the antiatherosclerotic effects of bisphosphonates are not mediated via PGE2, TXA 2, or COX-2, and the bisphosphonates do not interfere with the suppression of platelet COX-1 activity by ASA and COX-2 activity by nimesulide.
|Number of pages||7|
|Journal||Methods and Findings in Experimental and Clinical Pharmacology|
|Publication status||Published - júl. 1 2006|
ASJC Scopus subject areas
- Pharmacology (medical)