Intracellular calcium chelators and oxidant‐induced renal proximal tubule cell death

The effect of intracellular calcium chelators on rabbit renal proximal tubule (RPT) cell death induced by t‐butyl hydroperoxide (TBHP) and H₂O₂ was examined. Preincubation of RPT suspensions with 50 μM QUIN 2/AM completely prevented TBHP (0.5 mM) and H₂O₂ (2 mM) induced cell death [i.e., release of lactate dehydrogenase (LDH)]. QUIN 2/AM, BAPTA/AM, EGTA/AM, and FURA 2/AM, at 5 μM, decreased LDH release (at 6 hr) from 41% to 4%, 21%, 26%, and 33%, and decreased lipid peroxidation (at 1 hr) from 1.0 to 0.1, 0.4, 0.6, and 0.8 nmol MDA/mg protein, respectively, after TBHP exposure. Since oxidant‐induced lipid peroxidation and cell death are iron‐dependent in this model, these results suggest that the intracellular calcium chelators inhibit cell death by chelating iron.