Kidney trace metal response to combined cisplatin (CDDP) and hyperthermia

The effects of hyperthermia (HY) on cisplatin (CDDP) nephrotoxicity and kidney metal concentrations were evaluated in female F344 rats. Rats were anaesthetized with a xylazine/ketamine mixture, heated on a water-bed for 1 h to an intraperitoneal temperature of 41.1 +/- 0.2 degrees C, and maintained at hyperthermia for an additional 30 min (HY plateau). CDDP (5 mg/kg body weight) was administered at the start of the heating or at the HY plateau. Neither HY alone nor CDDP (5 mg/kg) at normothermia produced a significant effect on weight loss or nephrotoxicity. CDDP administered at the start of heating produced a moderate 1.5-fold increase in serum urea nitrogen (SUN) and serum creatinine concentrations. CDDP administered at the HY plateau produced a significant six-fold increase in SUN and a four-fold increase in creatinine concentration. Weight loss increased two- to three-fold from the combined regimen, but only the rats given CDDP at the HY plateau continued to lose weight through day 7. A loss of kidney copper (50-60%) resulted from the combined regimen, similar to losses observed with higher doses of CDDP at normothermia. HY alone had little effect on concentrations of kidney copper or zinc up to 4 days post-treatment. The results demonstrate that systemic hyperthermia significantly increases CDDP nephrotoxicity in F344 rats and that kidney copper loss from CDDP exposure at hyperthermia is similar to the loss observed from CDDP at normothermia.