Synergistic increase in cell lethality by dieldrin and H2O2 in rat thymocytes: Effect of dieldrin on the cells exposed to oxidative stress

Dieldrin, one of persistent pesticides, is highly resistant to biotic and abiotic degradation. It is accumulated in organisms. Recent studies suggest that dieldrin exerts a potent cytotoxic action on cells exposed to oxidative stress. In this study, the effect of dieldrin on rat thymocytes exposed to hydrogen peroxide (H₂O₂)-induced oxidative stress was examined. Dieldrin at 5 μM and H₂O₂ at 300 μM slightly increased cell lethality from a control value of 5.4 ± 0.5% (mean ± standard deviation of four experiments) to 7.8 ± 1.3% and 9.0 ± 0.3%, respectively. Simultaneous application of dieldrin and H₂O₂ significantly increased cell lethality to 46.2 ± 1.8%. The synergistic increase in cell lethality was dependent on dieldrin concentration (0.3–5 μM) but not on H₂O₂ concentration (30–300 μM). Dieldrin accelerated H₂O₂-induced cell death, which was estimated with the help of annexin V-FITC and propidium iodide. Presence of either dieldrin or H₂O₂ decreased the cellular content of nonprotein thiol and increased intracellular Zn²⁺ concentration. The combination of dieldrin and H₂O₂ further pronounced these effects. TPEN, a chelator of intracellular Zn²⁺, significantly attenuated the synergistic increase in cell lethality induced by dieldrin and H₂O₂. It is, therefore, suggested that dieldrin augments the cytotoxicity of H₂O₂ in a Zn²⁺-dependent manner.