ABSTRACT
We investigated the effect on human platelet aggregation of the naturally occurring quinone/hydroquinone couple, avarone and avarol. Avarone exerted antiplatelet activity both on platelet-rich plasma and, to a greater extent, on washed platelets. The quinone inhibited the platelet aggregatory process with all the agonists used. The highest inhibitory potency occurred with arachidonic acid or A23187 as stimulating agents. In the case of agonists such as adenosine 5' diphosphate, platelet-activating factor or U46619, the antiaggregatory effect was more pronounced on the second wave. Inhibition of the aggregatory process paralleled thromboxane B2 formation. Avarol also exerted antiplatelet activity, even though its inhibitory potency was much lower than that of avarone.
Subject(s)
Antineoplastic Agents/pharmacology , Blood Platelets/drug effects , Platelet Aggregation Inhibitors/pharmacology , Sesquiterpenes/pharmacology , Adenosine Diphosphate/pharmacology , Arachidonic Acid/pharmacology , Blood Platelets/metabolism , Cyclohexenes , Humans , Thromboxane B2/biosynthesisABSTRACT
Nitroarenes are environmental contaminants produced during incomplete combustion processes. It has been reported that nitroreduction, the most important pathway of nitroarene toxification, occurs mainly in the liver and intestine. In the present study we have shown that red cells also possess the metabolic competence to reduce nitroarenes. In particular, 1,8-dinitropyrene, the nitroarene chosen as model compound, was reduced to the corresponding mono- and diamino-derivatives, 1-amino-8-nitropyrene and 1,8-diaminopyrene, by human lysate supplemented with cofactors.
Subject(s)
Erythrocytes/metabolism , Pyrenes/metabolism , Humans , Oxidation-ReductionABSTRACT
In the present study we have shown that erythrocyte-catalyzed 1,8-dinitropyrene reduction occurs via formation of reactive intermediate species, which bind covalently to haemoglobin and other erythrocyte proteins. In fact after mild-acid hydrolysis of lysate proteins exposed to DNP, the reduced metabolites, 1-amino-8-nitropyrene and 1,8-diaminopyrene, were released, thus indicating the formation of sulphinamide adducts to proteins. These results suggest that haemoglobin adduct biomonitoring would be a useful method of controlling exposure to nitroarene in persons at risk.