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.