Effect of cephaloridine on respiration by renal cortical mitochondria

The effects of the nephrotoxic antibiotic, cephaloridine, were studied in rabbit renal cortical mitochondria. Mitochondria from animals which received a toxic dose of 200 mg/kg of the drug 2 hr before sacrifice (in vivo exposure) had significantly decreased rates of respiration compared with those of mitochondria from untreated control animals. In vitro exposure of normal mitochondria to cephaloridine resulted in a qualitatively similar decrease of respiration. With both in vivo and in vitro exposure, inhibition was greatest with ADP-dependent respiration using succinate as substrate. The severity of in vitro inhibition of respiration showed some correlation to the degree of in situ cytotoxicity at different cephaloridine concentrations. The results are in agreement with the finding of a reduction of rates of respiration in renal tubule suspensions after similar in vivo and in vitro exposure to cephaloridine. These studies provide preliminary evidence that cephaloridine nephrotoxicity may be mediated through an inhibitory effect on mitochondrial respiration.