Fort F L, Pratt M C, Carter G W, Lewkowski J P, Heyman I A, Cusick P K, Kesterson J W
Fundam Appl Toxicol. 1984 Apr;4(2 Pt 1):216-20. doi: 10.1016/0272-0590(84)90122-2.
Sprague-Dawley CD strain rats were given 18, 35, 70, or 140 mg/kg/day of 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline by gavage for 2 weeks. Heinz bodies were seen in the erythrocytes of rats given 140 mg/kg/day. Dose-related increases in methemoglobin were found at 35 mg/kg/day or more. Hemolytic anemia was characterized by dose-related decreases in hematocrit, hemoglobin, and total erythrocyte count. Reticulocytosis, decreased myeloid:erythroid ratio, splenomegaly, extramedullary hematopoiesis, increased serum total bilirubin, and icterus were also observed. This compound was found to oxidize oxyhemoglobin to methemoglobin in vitro, suggesting that the parent compound is capable of causing the hematological changes observed in vivo without conversion to active metabolites.
将斯普拉格-道利CD品系大鼠通过灌胃给予18、35、70或140毫克/千克/天的3-氨基-1-[间-(三氟甲基)苯基]-2-吡唑啉,持续2周。在给予140毫克/千克/天的大鼠红细胞中可见海因茨小体。在35毫克/千克/天及以上剂量时发现高铁血红蛋白呈剂量相关性增加。溶血性贫血的特征是血细胞比容、血红蛋白和总红细胞计数呈剂量相关性降低。还观察到网织红细胞增多、髓系:红系比例降低、脾肿大、髓外造血、血清总胆红素增加和黄疸。发现该化合物在体外可将氧合血红蛋白氧化为高铁血红蛋白,这表明母体化合物能够在不转化为活性代谢物的情况下引起体内观察到的血液学变化。