Antiemetic effect of dexamethasone on cisplatin-induced early and delayed emesis in the pigeon

Abstract

We investigated the ability of dexamethasone to attenuate cisplatin (4 mg/kg, i.v.)-induced early and delayed emesis. These appear within the first 8-h period (early phase) and between 8 and 48 h (delayed phase), respectively, after cisplatin administration in the pigeon. Dexamethasone (0.1 and 1 mg/kg, i.m.) reduced significantly the number of emetic responses to cisplatin by 56% and 82% ( P<0.05), respectively, in the early phase, and by 41% and 66% ( P<0.05), respectively, in the delayed phase. Dexamethasone (1 and 10 μg/kg, i.c.v.) reduced the number of emetic responses by 66% and 91% ( P<0.05), respectively, in the early phase, and by 56% and 87% ( P<0.05), respectively, in the delayed phase. Indomethacin (10 mg/kg, i.m.) did not suppress cisplatin-induced early and delayed emesis. Dexamethasone (1 mg/kg, i.m.) did not affect the content of platinum in the medulla oblongata after cisplatin administration. The above results suggest that dexamethasone has antiemetic effects on both the early and delayed emetic responses to cisplatin in pigeons, partially via its central site of action, and that the antiemetic mechanism of dexamethasone is related to factors other than its inhibition of prostanoid synthesis or its membrane stabilizing effect which reduces influx of cisplatin into the medulla oblongata.