Effects of pegylated recombinant human megakaryocyte growth and development factor on 5-fluorouracil-induced thrombocytopenia in balloon-injured rats.
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.
Harada
K
K
Pharmaceutical Development Laboratory, Kirin Brewery Co. Ltd, Maebashi, Gunma, Japan.
Tazunoki
Y
Y
Ide
Y
Y
Takeuchi
A
A
Kawahara
J
J
Suzuki
T
T
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D002404:Catheterization; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*; D013926:Thrombopoietin / Q000494:pharmacology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood / Q000187:drug effects; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin; D005472:Fluorouracil