Platelet activating factor (PAF) involvement in endotoxin-induced thrombocytopenia in rabbits: studies with FR-900452, a specific inhibitor of PAF |
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| Authors: | M Okamoto K Yoshida M Nishikawa M Kohsaka H Aoki |
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| Institution: | 1. Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India;2. Department of Studies in Molecular Biology, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India;3. College of Health Sciences, Kaohsiung Medical University, Vascular and Medicinal Research, Kaohsiung, 80708, Taiwan;4. Vascular and Medicinal Research, Texas Heart Institute, Houston, Texas 77030, USA;1. Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru 570006, Karnataka, India;2. Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD 21702, USA;3. Department of Studies in Molecular Biology, University of Mysore, Manasagangothri, Mysuru 570006, Karnataka, India;1. Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, India;2. Division of Biochemistry, School of Life Sciences, JSS Academy of Higher Education and Research, Mysore, India;3. Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore, India |
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| Abstract: | PAF (1 ug/kg) injected intravenously (i.v.) into anesthetized rabbits resulted in marked loss of circulating platelets and leukocytes. Administration of FR-900452 1-methyl-3-(1-(5-methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-y lidene)- 2-piperazinyl) ethyl)-2-indolinone, a specific PAF inhibitor, at a dose of 10 mg/kg i.v. with 10 min prior to the PAF injection significantly prevented both changes. On the other hand, PAF has been considered as a mediator of endotoxin shock. Therefore, in order to determine whether endogenous PAF contributes to the occurrence of thrombocytopenia or leukopenia in endotoxin shock, we assessed the effect of FR-900452 on the thrombocytopenia and the leukopenia following bolus i.v. injection of E.coli endotoxin (0.03 mg/kg) in rabbits. As a result, pretreatment with the compound (10 mg/kg, i.v.) significantly reduced the thrombocytopenia at 60 and 180 min after the endotoxin injection. In contrast, FR-900452 did not reduced the leukopenia at any time of after endotoxin. These results indicate that PAF might be involved in the occurrence of thrombocytopenia in rabbit endotoxemia and the contribution of PAF to the leukopenia is much less extent than that to the thrombocytopenia. |
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