The liquid culture filtrates of entomogenous fungus Paecilomyces tenuipes and its glycoprotein constituent protects against anemia in mice treated with 5-fluorouracil.
The purpose of the present study was to investigate the efficacy of a liquid culture filtrates of the entomogenous fungus Paecilomyces tenuipes (PTCF) and its main active glycoprotein-enriched (PGF) fraction against hematotoxicity in mice treated with 5-fluorouracil (5-FU). Oral administration of PTCF (100 mg/kg/d) for 7 consecutive days after 5-FU injection significantly suppressed reductions in the red and white blood cell counts in peripheral blood, and accelerated their recoveries. From PTCF, glycoprotein-enriched fraction (PGF, >90% protein, approximately 15 kDa determined by SDS-PAGE) was separated as active ingredient that ameliorates 5-FU-induced anemia. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of trypsinized-PGF showed 11 fragment ion peaks. Effective recoveries of erythrocytopenia and leukocytopenia were observed when PGF was co-administered with murine recombinant erythropoietin (mrEPO; 5 U/mouse). Oral administration of PGF also inhibited 5-FU-induced decreases in peripheral reticulocyte and bone marrow cell counts on day 12, and markedly hastened their recoveries on day 20, in dose-dependent manners. Reductions in erythroid progenitor colonies, such as colony-forming units (CFU)-erythroid and burst-forming units-erythroid mix, formed by bone marrow cells from 5-FU-treated mice were markedly improved by oral administration of PGF with subcutaneous mrEPO. Oral administration of PGF also increased the myeloid lineage progenitor, CFU-granulocyte-macrophages, in cultured bone marrow cells. These findings suggest that PGF isolated from P. tenuipes has the potential to protect against 5-FU-inudced erythrocytopenia and leukopenia, especially in combination with mrEPO, and also has hematopoietic activity, through stimulation of immature erythroid as well as myeloid progenitor cell differentiation.
Takata
Takanobu
T
Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan.
Tanaka
Tomoaki
T
Yahagi
Nobuo
N
Yahagi
Remiko
R
Tsuchida
Hideyuki
H
Ishigaki
Yasuhito
Y
Tomosugi
Naohisa
N
Fushiya
Shinji
S
Takano
Fumihide
F
Ohta
Tomihisa
T
D000740:Anemia / Q000139:chemically induced* / Q000517:prevention & control*; D000818:Animals; D000963:Antimetabolites; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003114:Colony-Forming Units Assay; D003470:Culture Media / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D005374:Filtration; D005472:Fluorouracil; D006023:Glycoproteins / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010143:Paecilomyces / Q000737:chemistry*; D011994:Recombinant Proteins; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000963:Antimetabolites; D003470:Culture Media; D006023:Glycoproteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D005472:Fluorouracil