Zinc increases vulnerability of rat thymic lymphocytes to arachidonic acid under in vitro conditions

Previous studies on the cytotoxicity of arachidonic acid (ARA) elucidated the involvement of oxidative stress and Ca2+. In the present study, the Zn2+-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 Zn2+ by Zn2+ chelators attenuated the ARA-induced increase in cell lethality. Thus, Zn2+ is suggested to be involved in ARA cytotoxicity. ARA at 3-10 μM elevated intracellular Zn2+ level. The Zn2+ chelators attenuated the ARA-induced increase in intracellular Zn2+ level while ARA significantly increased intracellular Zn2+ level in the presence of 3 μM ZnCl2, suggesting the involvement of external Zn2+. Zn2+ reportedly exerts cytotoxic action under oxidative stress induced by hydrogen peroxide, via an excessive increase in intracellular Zn2+ levels. Since ARA induces oxidative stress, the simultaneous administration of zinc and ARA may be harmful.