Measures against side effects of chemotherapy for head and neck cancer

We experimentally evaluated the usefulness of prostaglandin E1 (PGE1) in a model of cisplatin (CDDP)-induced nephrotoxicity. CDDP (6.5mg/kg) was intravenously injected in male Sprague-Dawley rats. PGE. was intravenously infused at different times and for different durations, and the following results were obtained:1. Infusion of PGE. (0.1μg/kg/min) for 4 hours from 15 minutes before CDDP injection inhibited decreases in blood urea nitrogen, serum creatinine, fractional excretion of sodium, and creatinine clearance. The nephrotoxic effects of CDDP were thus reduced.2. With PGE. infusion for 2 hours from 2 hours after CDDP administration, the effects was similar to those of PGE. infusion for 4 hours after CDDP injection. This suggested that PGE reduces the nephrotoxic effects of CDDP by inhibiting the renin-angiotensin system in the kidneys, there by maintaining renal hemodynamics. In addition, reabsorption and time factors in the pharmacokineties of CDDP seem to be involved.3. PGE1 infusion for 4 hours before CDDP injection significantly reduced the fractional excretion of sodium, as compared with PGE1infusion for 4 hours after CDDP injection, and also reduced the renal platinum level. These findings suggest that PGE1 prevented renal tubular cell destruction by cytoprotection, resulting in the inhibition of platinum accumulation. These results suggest that PGE1 reduces CDDP-induced renal toxicity. In addition, PGE1 is a bioactive substance and has few side effects. When given in an appropriate dose and at an appropriate time, PGE. may be useful in the prevention of CDDP-induced renal toxicity.