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.

Human thrombopoietin reduces myocardial infarct size, apoptosis, and stunning following ischaemia/reperfusion in rats

“…21,22 In initial human trials of Tpo, doses of 1-5 μg/kg increased platelet production five to 10 times in healthy individuals and in those about to receive chemotherapy for malignancy. Similarly in rats, the dose of PEGylated Tpo used to reduce thrombocytopenia (100 μg/kg) 23 and to ameliorate thrombocytopenia in carboplatin-treated rats (1-30 μg/kg) 24 is also considerably higher than the dose used in our study. The single dose of Tpo (0.05 or 1.0 μg/kg) we used did not result in an increased platelet count or haematocrit over the 16-day follow-up period.…”