Chronic effect of whole-body hyperthermia combined simultaneously with cis-diamminedichloroplatinum (II) on normal tissue in rat

Abstract

Long-term effects of cisplatin (DDP) (6 mgikg) alone at 37°C and DDP (2 mg/kg) plus whole body hyperthermia 120 min at 41.5°C) on DDP-mediated normal tissue toxicities were compared up to 12 months post-treatment using a F344 rat model. Acute renal damage, represented by an increase in blood urea nitrogen (BUN) at day 5 post-treatment, was significantly higher after DDP (6 mg/kg) alone at 37°C than the increase in BUN after DDP (2 mg/kg) plus whole body hyperthermia. After recovery, BUN levels as a result of both treatments remained elevated. From 9 months onwards BUN levels as a result of the combined treatment gradually increased to values > 100 mgidl. At 12 months, side toxicities as a result of the combined treatment were more severe than the side effects noted after DDP (6 mg/kg) alone at 37°C. Red blood cell and hematocrit values were significantly reduced, whereas BUN was significantly increased. The results obtained with histological examination of the kidneys corresponded with the observed functional differences. Platinum levels in the kidney, however, were highest in the DDP (6 mg/kg) alone at 37°C group. This observation does not explain why the chronic toxicity as a result of the combined modality treatment was more severe.

Key Words:

• Cis-platinum
• whole-body hyperthermia
• renal toxicity
• tissue distribution