Recombinant human granulocyte colony-stimulating factor accelerates regeneration after T-2 toxin-induced hemopoietic injury and lessens lethality in mice.
The effects of rhG-CSF on T-2-induced leukopenia and lethal toxicity in mice were investigated. First, T-2 was administered by gavage to adult male mice at a dose of 3 mg/kg b.w. daily for 7 days, and rhG-CSF was given i.p. in daily dose of 10 or 30 micrograms/kg b.w./day, beginning on the 2nd day, for 5 days. The peripheral WBC of mice receiving T-2 alone was decreased to one fourth of control counts, and bone marrow (BM) cell counts were also markedly diminished. The administration of rhG-CSF prevented those T-2-induced depressions. Histologically, the delation of the hematopoietic cells from BM and spleen of mice given T-2 was remarkably counteracted by administration of rhG-CSF. In the other experiment, rhG-CSF was injected i.p. for 5 days beginning on the next day of the 7-day T-2 administration. The recovery of WBC and BM cell counts was hastened by rhG-CSF reaching the control level in 6 days, and differential leukocyte analysis revealed an increase of neutrophils. Furthermore, simultaneous administration of rhG-CSF depressed the T-2-induced lethal toxicity, dose-dependently. The results revealed that rhG-CSF possesses a potent ability to protect T-2-induced leukopenia and lethality in mice, and it could be as an antidote against T-2 and related trichothecene-induced acute intoxication.
Ohtani
K
K
Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo.
Nanya
T
T
Aoyama
Y
Y
Matsunami
S
S
Sekijima
M
M
Kawamura
O
O
Ohtsubo
K
K
Ueno
Y
Y
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013605:T-2 Toxin / Q000633:toxicity*
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013605:T-2 Toxin