Effect of verapamil on cephaloridine nephrotoxicity in the rabbit

Cephaloridine produces proximal tubular necrosis in the rabbit kidney. Calcium channel blockers have ameliorated tissue injury due to toxic and ischemic insults. To determine whether renal damage caused by cephaloridine could be modified by pretreatment with verapamil, groups of rabbits were given cephaloridine, 100 mg/kg sc, 90 min after administration of verapamil, 200 micrograms/kg iv. Histologic scoring of the extent of proximal tubular necrosis 48 h later demonstrated increased necrosis in the group receiving verapamil plus cephaloridine. Verapamil pretreatment increased the concentration of cephaloridine in the renal cortex at 0.5 hr, but did not alter the peak concentration (2 hr after the dose) or cortical concentrations at 1 or 3 hr. Assay of total calcium content in cortical mitochondria 2 hr after cephaloridine showed that verapamil pretreatment abolished the increased accumulation following cephaloridine administration. We conclude that verapamil does not protect renal proximal tubular cells from the toxic effect of cephaloridine, and that verapamil prevents the cephaloridine-induced uptake of calcium by cortical mitochondria.