Ohno H, Tojo H, Kakihata K, Nomura M, Takayama S
Drug Safety Research Center, Developmental Research Laboratories, Daiichi Pharmaceutical Company Ltd., Tokyo R & D Center, Japan.
Fundam Appl Toxicol. 1993 Feb;20(2):141-6. doi: 10.1006/faat.1993.1019.
DQ-2511, a new anti-ulcer drug, was administered to beagle dogs for 4 weeks to investigate the mechanism whereby this drug induced hemolytic anemia and its reversibility in comparison with beta-acetylphenylhydrazine. Hemolytic anemia accompanied by an increase in the number of cells containing Heinz bodies that was preceded by a marked decrease in blood-reduced glutathione concentration was observed in dogs receiving 600 mg/kg of DQ-2511, but only a slight increase in the methemoglobin level was noted. beta-Acetylphenylhydrazine, however, caused hemolytic anemia accompanied by marked increases in both Heinz body-containing cells and methemoglobin concentration, but the blood-reduced glutathione concentration was not decreased consistently with the formation of Heinz bodies. Hemolytic anemia disappeared after a 4-week recovery period in the dogs that received DQ-2511. These results suggest that decreases in reduced glutathione in erythrocytes play an important role in the anemia and Heinz body formation induced by DQ-2511, but not by beta-acetylphenylhydrazine.
新型抗溃疡药物DQ - 2511对比格犬给药4周，以研究该药物诱发溶血性贫血的机制及其与β - 乙酰苯肼相比的可逆性。在接受600mg/kg DQ - 2511的犬中观察到溶血性贫血，伴有含海因茨小体的细胞数量增加，且在此之前血液中还原型谷胱甘肽浓度显著降低，但仅观察到高铁血红蛋白水平略有升高。然而，β - 乙酰苯肼导致溶血性贫血，伴有含海因茨小体细胞和高铁血红蛋白浓度均显著增加，但血液中还原型谷胱甘肽浓度并未随海因茨小体的形成而持续降低。接受DQ - 2511的犬在4周恢复期后溶血性贫血消失。这些结果表明，红细胞中还原型谷胱甘肽的减少在DQ - 2511诱发的贫血和海因茨小体形成中起重要作用，而在β - 乙酰苯肼诱发的过程中并非如此。
