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Zinc increases vulnerability of rat thymic lymphocytes to arachidonic acid under in vitro conditions
Institution:1. GLSynthesis Inc., One Innovation Drive, Worcester, MA 01605, USA;2. Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Edmond J. Safra Campus, Hebrew University, Jerusalem 91904, Israel;1. Laboratoire des sciences de l''ingénieur, de l''informatique et de l''imagerie, UMR 7357, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg/CNRS, 67412 Illkirch, France;2. Fluoptics, 38040 Grenoble, France;3. Institut Albert Bonniot, U-823, Université Joseph Fourier/INSERM, 38000 Grenoble, France;4. Centre Hospilato-Universitaire de Saint-Etienne, 42000 Saint-Etienne, France;5. CEA-LETI, Minatec, 38054 Grenoble, France;1. School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province 510310, China;2. Key Research Center of Liver Regulation for Hyperlipidemia SATCM/Class III Laboratory of Metabolism SATCM, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
Abstract: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.
Keywords:Arachidonic acid  Cytotoxicity  Lymphocyte  Oxidative stress  Zinc
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