Imai K, Matsuura M, Furukawa H, Hayashi Y
Nihon Yakurigaku Zasshi. 1975 Oct;71(7):691-707. doi: 10.1254/fpj.71.691.
Heinz body anemia was induced in dogs by consecutive oral administration of 200 mg/kg and 60 mg/kg of aminopyrine, 200 mg/kg of phenacetin and 5 mg/kg of acetylphenylhydrazine, for either 8 or 16 weeks. Biochemical analysis showed a decrease of haptoglobin in plasma and reduced-glutathion in red blood cells in association with anemia. Hematologically, an increase in osmotic fragility and cell volume of erythrocytes were also noted. Pathological examination revealed marked erythrophagia and hemosiderosis in the reticuloendothelial system of treated animals. A new anti-inflammatory analgesic 31252-S (3-(1-hydroxy-2-piperidinoethyl)-5-phenylisoxazole citrate) was also tested for the hemolytic effects in dogs. Blood analyses revealed a slight increase of Heinz bodies and a decrease of reduced-glutathion in red blood cells without anemia. These findings suggest that 31252-S have weaker oxidant properties than those of aminopyrine and phenacetin. The present studies showed that the concentration of reduced-glutathion in red blood cells of non-treated dogs was approximately 50% lower than that of the erythrocytes of normal human beings. This finding appeared to correspond with high susceptibility of red blood cells to hemolytic effects of oxidant-drugs in dogs.
通过连续8周或16周口服200mg/kg和60mg/kg的氨基比林、200mg/kg的非那西丁和5mg/kg的乙酰苯肼,在犬中诱发海因茨小体贫血。生化分析显示,血浆中触珠蛋白减少,红细胞中还原型谷胱甘肽减少,同时伴有贫血。血液学检查还发现,红细胞的渗透脆性和细胞体积增加。病理检查显示,受试动物的网状内皮系统存在明显的红细胞吞噬和含铁血黄素沉着。还对一种新型抗炎镇痛药31252-S(3-(1-羟基-2-哌啶基乙基)-5-苯基异恶唑柠檬酸盐)在犬中的溶血作用进行了测试。血液分析显示,海因茨小体略有增加,红细胞中还原型谷胱甘肽减少,但无贫血。这些发现表明,31252-S的氧化特性比氨基比林和非那西丁弱。本研究表明,未处理犬红细胞中还原型谷胱甘肽的浓度比正常人红细胞低约50%。这一发现似乎与犬红细胞对氧化药物溶血作用的高敏感性相符。