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Myelosuppression in the pig (Sus scrofa): uteroferrin reduces the myelosuppressive effects of 5-fluorouracil in young pigs.
- Source :
-
Comparative biochemistry and physiology. Part A, Physiology [Comp Biochem Physiol A Physiol] 1997 Apr; Vol. 116 (4), pp. 369-77. - Publication Year :
- 1997
-
Abstract
- The present study investigated the ability of uteroferrin to modulate the myelosuppressive effects of 5-fluorouracil (5-FU) in young pigs (Sus scrofa). Pigs (28-35 days of age; n = 6 per treatment) were infused with equal amounts of 5-FU on days 0 and 1 of the experimental period (37.5 mg/kg cumulative dose). Uteroferrin (100 micrograms/kg in 0.9% NaCl) or control (equivalent volume of 0.9% NaCl) was administered to pigs as intramuscular injections twice daily (08:00 and 20:00 hr) on days 1 through 21. Peripheral blood cell number, composition and progenitor cells were determined over 28 days. Treatment of pigs with 5-FU resulted in a rapid dose-dependent (P < 0.05) leukocytopenia. Concurrent treatment of pigs with uteroferrin reduced (P < 0.05) the rate of 5-FU-induced leukocytopenia (44 vs 77 +/- 7% decline from baseline on day 3) and enhanced (P < 0.05), the recovery from 5-FU on days 10 and 12 postinfusion. The positive effect of uteroferrin on leukocytes resulted primarily from a protection and/or enhanced recovery of neutrophils and monocytes. In addition, uteroferrin attenuated (P < 0.05) the suppression of red blood cell numbers after 5-FU administration (6.9 vs 6.1 +/- 0.2 x 10(6) cells/microliter on day 3), an affect reflected in increased hematocrit and hemoglobin concentrations. The effects of uteroferrin appeared to result from enhancement of the proliferation and/or differentiation of primitive pluripotent stem cells resistant to 5-FU, as concurrent treatment of pigs with uteroferrin resulted in a protection and/or enhanced recovery (P < 0.05) of CFU-GEMM, CFU-GM and BFU-E progenitor cells in the peripheral blood. These results are the first to demonstrate that uteroferrin can reduce the myelosuppressive effects of 5-FU in the pig and suggest that uteroferrin has hematopoietic growth factor activity in vivo.
- Subjects :
- Acid Phosphatase
Animals
Bone Marrow Cells
Dose-Response Relationship, Drug
Erythrocyte Count drug effects
Erythroid Precursor Cells drug effects
Hematocrit
Hematopoietic Stem Cells drug effects
Isoenzymes
Leukocyte Count drug effects
Leukopenia chemically induced
Male
Swine
Tartrate-Resistant Acid Phosphatase
Antimetabolites, Antineoplastic toxicity
Bone Marrow drug effects
Fluorouracil antagonists & inhibitors
Fluorouracil toxicity
Leukopenia prevention & control
Metalloproteins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-4940
- Volume :
- 116
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Comparative biochemistry and physiology. Part A, Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 9125688
- Full Text :
- https://doi.org/10.1016/s0300-9629(96)00368-4