Document Detail


Effects of bisphosphonates on prostaglandin E2 and thromboxane B2 production in human whole blood and monocytes stimulated by lipopolysaccharide and A23187.
MedLine Citation:
PMID:  16894405     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
O-M Tuominen; R Ylitalo-Heikkala; T I Vehmas; I Mucha; P Ylitalo; A Riutta
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2006-08-08     Completed Date:  2006-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909595     Medline TA:  Methods Find Exp Clin Pharmacol     Country:  Spain    
Other Details:
Languages:  eng     Pagination:  361-7     Citation Subset:  IM    
Affiliation:
Department of Pharmacological Sciences, Medical School, University of Tampere, Tampere, Finland.
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MeSH Terms
Descriptor/Qualifier:
Aspirin / 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:
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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