| Effects of bisphosphonates on prostaglandin E2 and thromboxane B2 production in human whole blood and monocytes stimulated by lipopolysaccharide and A23187. | |
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MedLine Citation:
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PMID: 16894405 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bisphosphonates are antiatherosclerotic, suppress monocyte-macrophages, and modulate proinflammatory mediators. Prostaglandin (PG) E(2), thromboxane (TX) A(2), 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 PGE(2) and TXB(2) production in human whole blood and monocytes. PGE(2) and TXB(2) were determined by direct radioimmunoassay and COX-2 expression by Western blot. In whole blood, the bisphosphonates did not modulate the increase in PGE(2) and TXB(2) concentrations induced by calcium ionophore A23187 or lipopolysaccharide (LPS). None of the bisphosphonates did change PGE(2) and TXB(2) concentration after spontaneous clotting. A23187- and spontaneous clotting-induced PGE(2) and TXB(2) productions were inhibited over 90% by acetylsalicylic acid (ASA), and LPS-induced PGE(2) and TXB(2) formations were inhibited over 90% by nimesulide. None of the bisphosphonates altered these inhibitions. In monocytes, etidronate and clodronate augmented A23187-stimulated PGE(2) production 2.5- to 3.2-fold (p < 0.05). LPS- or A2318-induced elevations in TXB(2) 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 PGE(2), 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. |
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Authors:
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O-M Tuominen; R Ylitalo-Heikkala; T I Vehmas; I Mucha; P Ylitalo; A Riutta |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Methods and findings in experimental and clinical pharmacology Volume: 28 ISSN: 0379-0355 ISO Abbreviation: Methods Find Exp Clin Pharmacol Publication Date: 2006 Jul-Aug |
Date Detail:
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Created Date: 2006-08-08 Completed Date: 2006-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7909595 Medline TA: Methods Find Exp Clin Pharmacol Country: Spain |
Other Details:
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Languages: eng Pagination: 361-7 Citation Subset: IM |
Affiliation:
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Department of Pharmacological Sciences, Medical School, University of Tampere, Tampere, Finland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aspirin
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pharmacology Blotting, Western Bone Density Conservation Agents / pharmacology* Calcimycin / pharmacology* Clodronic Acid / pharmacology Cyclooxygenase Inhibitors / pharmacology Dinoprostone / biosynthesis*, blood Diphosphonates / pharmacology* Etidronic Acid / pharmacology Female Humans Lipopolysaccharides / pharmacology* Lipoproteins, LDL / metabolism Male Monocytes / drug effects, metabolism* Radioimmunoassay Sulfonamides / pharmacology Thromboxane B2 / biosynthesis*, blood |
| Chemical | |
Reg. No./Substance:
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0/Bone Density Conservation Agents; 0/Cyclooxygenase Inhibitors; 0/Diphosphonates; 0/Lipopolysaccharides; 0/Lipoproteins, LDL; 0/Sulfonamides; 10596-23-3/Clodronic Acid; 2809-21-4/Etidronic Acid; 363-24-6/Dinoprostone; 50-78-2/Aspirin; 51803-78-2/nimesulide; 52665-69-7/Calcimycin; 54397-85-2/Thromboxane B2; 89987-06-4/tiludronic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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