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PAF Antagonists (paf + antagonist)
Selected AbstractsPossible involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressor responses to platelet activating factor (PAF) in ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2000Yoshio Tanaka In anaesthetized rats, platelet activating factor (PAF; 1 ,g kg,1) decreased mean arterial blood pressure by around 60 mmHg (n=18). This depressor response was completely blocked by the PAF antagonist, CV-6209 (1 mg kg,1), indicating the role of PAF-specific receptor in the response. NG -nitro- L -arginine methyl ester (L -NAME; 50 mg kg,1), an NO synthase inhibitor, profoundly elevated systemic blood pressure (n=19), indicating an important role of NO in the basal blood pressure regulation. The depressor response to PAF (1 ,g kg,1) normalized against that to sodium nitroprusside (SNP) (10 ,g kg,1) was not substantially different between rats treated without and with L -NAME (n=4). In contrast, the depressor effect of acetylcholine (0.03,1.0 ,g kg,1) normalized against that of SNP (10 ,g kg,1) was significantly attenuated by L -NAME (n=5). Charybdotoxin (0.4 mg kg,1) plus apamin (0.2 mg kg,1) significantly attenuated the depressor response to PAF (1 ,g kg,1) (n=5) without affecting the blood pressure change due to SNP (1 mg kg,1) (n=3). Charybdotoxin (0.4 mg kg,1) (n=4) or apamin (0.2 mg kg,1) (n=4) alone did not affect the PAF-induced depressor response. These findings suggest that EDHF may make a significant contribution to the depressor response to PAF in rats. Although NO plays the determinant role in the basal blood pressure regulation, its contribution to PAF-produced depressor response seems to be less as compared with that to the depressor response to acetylcholine. British Journal of Pharmacology (2000) 131, 1113,1120; doi:10.1038/sj.bjp.0703681 [source] BIOACTIVE POLAR LIPIDS IN OLIVE OIL, POMACE AND WASTE BYPRODUCTSJOURNAL OF FOOD BIOCHEMISTRY, Issue 4 2008HARALABOS C. KARANTONIS ABSTRACT Olive oil protects against atherosclerosis because of biologically active microconstituents. In this study, total polar lipids from olive oil, pomace, pomace oil and waste byproducts were extracted, fractionated by thin layer chromatography and tested for their bioactivity. The most active ones were further purified on high-performance liquid chromatography, and the resulting lipid fractions were tested for their bioactivity. Bioactive compounds were determined in all samples with the exception of olive pomace oil. These lipids inhibited platelet-activating factor (PAF)-induced platelet aggregation and also induced platelet aggregation. The bioactive compound from olive pomace has been chemically characterized as a glycerylether-sn-2-acetyl glycolipid based on mass spectra. Chemical determinations and mass spectrometry data reinforce the assumption that these active microconstituents share both similar bioactivity and common structural features. The existence of PAF antagonists in polar lipid extracts from olive oil waste by-products render them biologically valuable materials for the food industry that could be used for the production of functional foods. PRACTICAL APPLICATIONS Isolated bioactive polar lipids from waste by-products of the olive oil industry that act as inhibitors of platelet-activating factor (PAF) may be used for enrichment and production of foods with higher nutritional value, as PAF plays a major role in inflammatory disorders, including atherosclerosis development. [source] The significance of platelet-activating factor and fertility in the male primate: a reviewJOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2005William E. Roudebush Abstract:, Since its discovery nearly 30 years ago platelet-activating factor (PAF) has emerged as one of the more important lipid mediators known. PAF (1- O -alkyl-2- O -acetyl- sn -glycero-3-phosphorylcholine) exists endogenously as a mixture of molecular species with structural variants of the alkyl moiety. PAF is a novel potent signaling phospholipid that has unique pleiotropic biological properties in addition to platelet activation. PAF also plays a significant role in reproduction and is present in the sperm of a number of primate species. PAF content in squirrel monkey sperm is significantly higher during the breeding season than the non-breeding season. PAF content in rhesus sperm has a significant relationship with sperm motility. PAF content in human sperm has a positive correlation with seminal parameters and pregnancy outcomes. The enzymes (lyso-PAF-acetyltransferase and PAF-acetylhydrolase) necessary for PAF activation and deactivation are present in primate sperm. PAF-acetylhydrolase may act as a ,decapacitation factor'. Removal of this enzyme during capacitation promotes PAF synthesis increasing primate motility and fertilization. PAF also plays a significant role in the fertilization process, enhancing the fertilization rates of oocytes. Enhanced embryo development has also been reported in oocytes fertilized with PAF-treated sperm. Exogenous PAF will also significantly improve primate artificial insemination pregnancy outcomes. PAF antagonists inhibit sperm motility, acrosome reaction, and fertilization thus suggesting the presence of receptors for PAF. The PAF-receptor is present on primate sperm, with altered transcript levels and distribution patterns on abnormal cells. Whereas, the exact mechanism of PAF in sperm function and reproduction is uncertain, its importance in normal primate fertility is substantial. [source] Antiatherogenic properties of lipid minor constituents from seed oilsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 12 2003Haralabos C Karantonis Abstract A number of lines of evidence suggest that seed oils exhibit a protective effect against atherogenesis. Most of the protective compounds are still unidentified. In this study, polar lipids of seed oil samples from sesame, corn and sunflower were successively fractionated by high-performance liquid chromatography. Each isolated lipid compound was tested in vitro for its ability to inhibit platelet-activating factor (PAF) and thrombin-induced washed rabbit platelet aggregation or to cause platelet aggregation. A significant number of lipids that exerted the above biological activities were detected. The most biologically active compounds were subjected to biological, chemical and spectroscopic analyses, and their structural data are presented. These results give a different explanation for the antiatherogenic action that seed oils exert. Given that PAF plays a pivotal role in atherogenesis, the fact that these oils contain PAF antagonists suggests their high nutritional value. Copyright © 2003 Society of Chemical Industry [source] Modulation of the pathology of late xenograft rejection by PAF-antagonist UR-12670 in the hamster-to-rat liver xenotransplant model,APMIS, Issue 3 2003PAF antagonist alleviates xenogeneic rejection PAF antagonists have been used in xenotransplantation to alleviate the pathogenesis of hyperacute rejection. This study evaluated the ability of the PAF antagonist UR-12670 to improve graft function in late xenograft rejection (LXR) in an orthotopic liver xenotransplantation model, and the involvement of PAF (platelet activating factor) in this type of rejection. The recipients of a hamster xenograft received standard immunosuppression (tacrolimus 0.2 mg/kg/30 days, MMF 25 mg/kg/8 days). Study groups: group A, without UR-12670, group B, UR-12670 (20 mg/kg/8 d) and group C, continuous administration of UR-12670 (20 mg/kg/d). Serum levels of xenoantibodies were evaluated by flow cytometry and tissue deposits by immunofluorescence. Immunoblot and indirect immunofluorescence assessed specificity of xenoantibodies. Conventional histology was performed. Continuous administration of UR-12670 improved the histological pattern of liver xenografts, especially necrosis, loss of hepatocytes, hemorrhage, sinusoidal congestion and lymphocyte infiltration. There was not a shift in specificity of xenoantibodies at different times posttransplantation, as demonstrated by immunoblotting and indirect immunofluorescence. UR-12670 administration had a beneficial effect on graft function and considerably improved the histopathological pattern, but it failed to induce tolerance after withdrawal of immunosuppression. UR-12670 had an immunomodulatory effect on cellular response but not on antibody production. There was not a change in the specificity of xenoantibodies produced at LXR compared with pretransplant antibodies. [source] | |||||||||||||