Previous studies on the cytotoxicity of arachidonic acid (ARA) elucidated the involvement of oxidative stress and Ca(2+). In the present study, the Zn(2+)-related cytotoxicity of ARA was studied by a flow cytometric technique with appropriate fluorescent probes in rat thymocytes. Addition of 10 μM ZnCl2 enhanced the increase in cell lethality induced by 10 μM ARA. The removal of Zn(2+) by Zn(2+) chelators attenuated the ARA-induced increase in cell lethality. Thus, Zn(2+) is suggested to be involved in ARA cytotoxicity. ARA at 3-10 μM elevated intracellular Zn(2+) level. The Zn(2+) chelators attenuated the ARA-induced increase in intracellular Zn(2+) level while ARA significantly increased intracellular Zn(2+) level in the presence of 3 μM ZnCl2, suggesting the involvement of external Zn(2+). Zn(2+) reportedly exerts cytotoxic action under oxidative stress induced by hydrogen peroxide, via an excessive increase in intracellular Zn(2+) levels. Since ARA induces oxidative stress, the simultaneous administration of zinc and ARA may be harmful.
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