title: Platelet hypersensitivity induced by 1-chloro-2, 4-dinitrobenzene, hydroperoxides and inhibition of lipoxygenase.
abstract: Platelets administered 1-chloro-2,4-dinitrobenzene to deplete intracellular glutathione (GSH) and inhibit GSH-peroxidase responded with irreversible aggregation to low doses of arachidonic acid (AA) more rapidly than control cells. This increase in sensitivity was correlated to inhibition of GSH-peroxidase, and not with the depletion of GSH. Addition of hydrogen peroxide, 15-hydroperoxyeicosatetraenoic acid, or inhibition of the lipoxygenase metabolic pathway by 4,7,10,13-eicosatetraynoic acid also induced a hypersensitive aggregation response to AA. These results suggest that the three modes of treatment share a common mechanism of increasing AA metabolism to biologically active prostaglandins and thromboxane A2 through alterations in cyclooxygenase kinetics and available enzyme substrate.
authors.affiliation: Cancer Research Center of Hawaii, University of Hawaii, Honolulu, 96813.
authors.forename: T D
authors.initials: TD
authors.lastname: Hill
authors.forename: J G
authors.initials: JG
authors.lastname: White
authors.forename: G H
authors.initials: GH
authors.lastname: Rao
mesh_terms: D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D004137:Dinitrochlorobenzene / Q000494:pharmacology*; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000494:pharmacology; D008054:Lipid Peroxides / Q000494:pharmacology; D008084:Lipoxygenase / Q000097:blood; D016859:Lipoxygenase Inhibitors; D010545:Peroxides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects
chemical_list: D004137:Dinitrochlorobenzene; D015289:Leukotrienes; D008054:Lipid Peroxides; D016859:Lipoxygenase Inhibitors; D010545:Peroxides; D015117:5,8,11,14-Eicosatetraynoic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D008084:Lipoxygenase; D005978:Glutathione