Cytotoxic activity of 13-hydroxyoctadecadienoic acid against Toxoplasma gondii.
Recent data indicate that platelets may play an important role in the host defence against Toxoplasma gondii infections. T. gondii-stimulated human platelets release thromboxane A2 (TXA2) and 12-hydroxyeicosatetraenoic acid (12-HETE) from arachidonic acid and 13-hydroxyoctadecadienoic acid (13-HODE) from linoleic acid (Yong et al. 1991; Henderson et al. 1992). We have previously demonstrated that the eicosanoid TXA2 has potent cytotoxic activity against T. gondii trophozoites (Yong et al. 1991). In this study, we examined whether 12-HETE, 13-HODE, and linoleic acid also have toxoplasmacidal activity. 13-HODE at concentrations > or = 10(-8) M rapidly induced cytotoxic changes in T. gondii. Ultrastructural changes induced by 13-HODE in T. gondii included an initial leakage of cytoplasmic contents into a space between the inner and outer parasite bilayer membrane units which was followed by intracellular vacuolation and loss of cytoplasmic contents. In contrast, linoleic acid and 12-HETE lacked toxoplasmacidal activity at 10(-10)-10(-6) M concentrations. These data indicate that 13-HODE, a product of linoleic acid metabolism, has potent cytotoxic activity against T. gondii; this toxoplasmacidal activity may be important in the inflammatory response to this pathogen.
Henderson
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Department of Medicine, University of Washington, Seattle 98195.
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D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008854:Microscopy, Electron; D014122:Toxoplasma / Q000187:drug effects* / Q000648:ultrastructure
D000991:Antithrombins; D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; C024348:13-hydroxy-9,11-octadecadienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D019787:Linoleic Acid