Influence of ondansetron on the antitumor activity and lung toxicity of bleomycin

ABSTRACT

Bleomycin [BLM] is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Moderate nausea and vomiting occur in virtually all patients taken BLM. Ondansetron [OND] is a highly selective 5-HT3 receptor antagonist with significant antiemetic activity. This study was conducted to investigate the effect of OND administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma [EAC] cells. Ondansetron did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5-HT and increase in the contractility of tracheal smooth muscles induced by ACh. The toxicity was also confirmed biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in GSH level. Pretreatment with ondansetron decreased lipid peroxidation and normalized GSH level and hence enhanced the percent survival of rats. The results of the present study indicate that OND did not modify the antitumor effect of BLM but ameliorated the increase in some biochemical markers associated with BLM-induced lung toxicity