Hisadome M, Fukuda T, Terasawa M, Oe T, Takahata H, Goto K, Tsuru S, Nomoto K
Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd, Fukuoka, Japan.
Int J Immunopharmacol. 1992 Oct;14(7):1195-201. doi: 10.1016/0192-0561(92)90055-p.
The effect of a novel synthetic compound, Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, on recovery from long-lasting leukopenia induced by 5-fluorouracil was compared with that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). When mice were administered i.p. with 5-FU (200 mg/kg) on days 0 and 7, intravenous administration of Y-25510 (100 and 1000 micrograms/kg) prevented the decrease in the peripheral leukocyte and neutrophil number and accelerated the recovery from leukopenia. Subcutaneous administration of rhG-CSF (50 micrograms/kg) did not prevent leukopenia but accelerated the recovery from leukopenia. In particular, peripheral neutrophil number increased over a normal level. The administration of Y-25510 (10, 100 and 1000 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, lymphocytes, neutrophils and monocytes. The administration of rhG-CSF (50 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, and neutrophils but not that of lymphocytes and monocytes. In fractions of bone marrow cells on day 21, the administration of Y-25510 (1000 micrograms/kg) showed a tendency of restoring the decrease in neutrophil number. In conclusion, the administration of Y-25510 prevented leukopenia and accelerated the recovery from leukopenia in the 5-FU-treated mice. It is suggested that the mechanism of the restorative action of Y-25510 is different from that of rhG-CSF. In a number of immature bone marrow cells Y-25510 has a potent stimulatory effect on the recovery from the decrease in number of hematopoietic cells, keeping a balance in number of each blood cell.
将一种新型合成化合物Y-25510（±）-3-[4-（2-二甲基氨基-1-甲基乙氧基）苯基]-1H-吡唑并[3,4-b]吡啶-1-乙酸对5-氟尿嘧啶诱导的持续性白细胞减少症恢复的影响与重组人粒细胞集落刺激因子（rhG-CSF）进行了比较。在第0天和第7天给小鼠腹腔注射5-氟尿嘧啶（200mg/kg）后，静脉注射Y-25510（100和1000μg/kg）可防止外周白细胞和中性粒细胞数量减少，并加速白细胞减少症的恢复。皮下注射rhG-CSF（50μg/kg）不能预防白细胞减少症，但能加速白细胞减少症的恢复。特别是，外周中性粒细胞数量增加超过正常水平。给予Y-25510（10、100和1000μg/kg）可恢复骨髓细胞、脾细胞、淋巴细胞、中性粒细胞和单核细胞数量的减少。给予rhG-CSF（50μg/kg）可恢复骨髓细胞、脾细胞和中性粒细胞数量的减少，但不能恢复淋巴细胞和单核细胞数量的减少。在第21天的骨髓细胞组分中，给予Y-25510（1000μg/kg）显示出恢复中性粒细胞数量减少的趋势。总之，给予Y-25510可预防5-氟尿嘧啶处理小鼠的白细胞减少症并加速白细胞减少症的恢复。提示Y-25510的恢复作用机制与rhG-CSF不同。在许多未成熟骨髓细胞中，Y-25510对造血细胞数量减少的恢复具有强大的刺激作用，保持各血细胞数量的平衡。
