Effects of pegylated recombinant human megakaryocyte growth and development factor on 5-fluorouracil-induced thrombocytopenia in balloon-injured rats.

Abstract

We examined whether pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) affected 5-fluorouracil-induced thrombocytopenia without inducing more severe intimal thickening after injury to rat carotid arteries. Rat carotid arteries were injured using a balloon catheter on day 0. 5-Fluorouracil (100 mg kg(-1)) or vehicle was intravenously administered on day 1 in balloon-injured rats. PEG-rHuMGDF (100 microg kg(-1)) or vehicle was intravenously administered once a day on days 1-5 to balloon-injured rats given 5-fluorouracil or vehicle. 5-Fluorouracil (100 mg kg(-1), i.v.) caused a significant decrease in the platelet count from day 3 and peaked on days 7-9 in balloon-injured rats. PEG-rHuMGDF (100 microg kg(-1), i.v.) reduced this decrease on days 9 and 11. The administration of PEG-rHuMGDF did not accelerate the intimal thickening of balloon-injured arteries in rats treated with 5-fluorouracil compared with control balloon-injured rats. PEG-rHuMGDF did not increase plasma tumour growth factor-beta1 (TGF-beta1) from days 0-9 in balloon-injured rats compared with control balloon-injured rats. These results suggest that PEG-rHuMGDF ameliorated 5-fluorouracil-induced thrombocytopenia without accelerating the intimal thickening of balloon-injured arteries.