ABSTRACT
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 5µM and H2O2 at 300µM 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 (0.3-5µM) but not on H2O2 concentration (30-300µM). 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 Zn(2+) concentration. The combination of dieldrin and H2O2 further pronounced these effects. TPEN, a chelator of intracellular Zn(2+), 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 Zn(2+)-dependent manner.
