Re(I) tricarbonyl complex of 1,10-phenanthroline-5,6-dione: DNA binding, cytotoxicity, antiinflammatory and anti-coagulant effects towards platelet activating factor

The complex fac-[Re(CO)3(phendione)Cl] (1) (where phendione = 1,10-phenanthroline-5,6-dione) has been synthesized and fully characterized by UV–visible, FTIR, and NMR techniques. The DNA binding properties of 1 are investigated by UV-spectrophotometric (melting curves), covalent binding assay, CV (cyclic voltammetry), circular dichroism (CD) and viscosity measurements. Experimental data indicate that 1 fits into the major groove without disrupting the helical structure of the B-DNA in contrast to the free phendione which intercalates within the base pairs of DNA. Upon irradiation, complex 1promotes the cleavage of plasmid pBR322 DNA from supercoiled form I to nicked form II via a proton coupled electron transfer mechanism. This comes as a result of experimental data in anaerobic/aerobic conditions and in the presence of DMSO. The biological activities of 1 and its precursors [Re(CO)5Cl] and phendione are tested towards a series of cancerous cell lines as glioblastoma (T98G), prostate cancer (PC3) and breast cancer (MCF-7) as well as platelet activating factor (PAF)-aggregation. Moreover, all the aforementioned compounds are tested for their ability to modulate PAF-basic metabolic enzyme activities in preparations of rabbit leukolytes. The in vitro experiments indicate that phendione has a better antitumor effect than cisplatin whereas [Re(CO)5Cl] is a better PAF inhibitor than both the phendione ligand and 1. Moreover, for the first time it is indicated that [Re(CO)5Cl], with a IC50 of 17 nM is comparable to the widely used PAF receptor antagonists, BN52021 and WEB2170 with IC50 of 30 and 20 nM, respectively, whereas 1 affects PAF-catabolism

Consumption of Farmed Fish, Fed with an Olive-Pomace Enriched Diet, and Its Effect on the Inflammatory, Redox, and Platelet-Activating Factor Enzyme Profile of Apparently Healthy Adults: A Double-Blind Randomized Crossover Trial

A fish-rich diet has a beneficial effect on cardiovascular health. The platelet activating factor (PAF) is involved in the development of atherosclerosis, and in vitro results support the regulating action of bioactive nutrients on PAF metabolism. The purpose of this study is to examine whether the consumption of farmed fish fed with an olive-pomace enriched diet (EF) affects PAF metabolism and the markers of inflammation and oxidative stress compared to the consumption of conventionally fed farmed fish (CF). Thirty apparently healthy adults completed a randomized double-blind crossover trial, during which they consumed both CF and EF twice a week for 8 weeks with a six-week washout period in between. The activities of PAF acetylhydrolase (PAF-AH), lysoPAF acetyltransferase (lysoPAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol-choline-phosphotransferase (PAF-CPT) in leukocytes, and lipoprotein-associated phospholipase A2 (LpPLA2) in serum were determined. The quantities of interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP), oxidized LDL (ox-LDL), thiobarbituric acid-reactive substances (TBARS), and glutathione peroxidase (GPx), as well as the serum oxidation, were also determined. Both types of fish exerted similar effects as there were no statistically significant differences between the two interventions except for an elevated PAF-CPT and reduced arachidonic acid (AA) in the red blood cell (RBC) membrane lipids after the EF intake

Platelet activating factor levels and metabolism in tangier disease: a case study

Abstract Background Tangier disease (TD) is a phenotypic expression of rare familial syndrome with mutations in the ABCA1 transporter. The risk of coronary artery disease in patients with TD is variable. On the other hand the pivotal role of Platelet-Activating Factor (PAF) mediator in atheromatosis was found. Plasma lipoproteins are transporters of the PAF acetylhydrolase (PAF-AH) in cells and known as lipoprotein-phospholipase A2 (Lp-PLA2) in plasma and regulators of PAF levels in blood. In addition, PAF can be biosynthesized from the remodeling and the de novo pathways in which Lyso-platelet activating factor-acetyltransferase (Lyso-PAF-AT) and platelet activating factor-cholinephosphotransferase (PAF-CPT) are the regulatory enzymes. The aim of this study is to investigate in a TD patient with a unique mutation (C2033A), the concentration of PAF in blood, the Equivalent Concentration for 50% aggregation (EC50) values of platelet rich plasma (PRP) toward PAF, adenosine diphosphate (ADP) and thrombin, and the activities of PAF metabolic enzymes Lp-PLA2, PAF-AH, Lyso-PAF-AT and PAF-CPT. Methods The EC50 value of PRP was measured by an aggregometer. The determination of the specific activity of PAF-CPT and Lyso-PAF-AT was made after in vitro enzymatic assay, chromatographic separation and measurement of the produced PAF in a biological assay with washed rabbit platelets. The determination of PAF-AH and Lp-PLA2 was made after an in vitro enzymatic assay from the decay of radioactive PAF. Results The TD patient had lower bound-PAF values in blood, decreased specific activity of PAF-CPT and Lyso-PAF-AT, increased specific activity of PAF-AH in platelets and leukocytes and Lp-PLA2 activity in plasma compared to healthy women. The EC50 of PAF and Thrombin were higher compared to healthy women. Conclusion The increased Lp-PLA2 activity, as well as, the decreased activities of PAF-CPT and Lyso-PAF-AT, explain the decreased bound-PAF level in TD patient and the EC50 of PAF. However, total PAF is in a normal range and this probably can explain one of the reasons this TD patient has no CAD.</p