Ni Y C, Xu Y Q
Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine.
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 1990;8(4):256-9.
The in vitro metabolic system comprised NADP co-factors and liver microsomes isolated from male rats pre-treated with phenobarbital, 60 mg/kg, i.p. for 3d combined with a single i.p. dose of 80 mg/kg of naphtholflavone. The 1% RBC suspension was made up from G6PD-deficient rabbit blood. Primaquine, chloroquine and M 8506 at various dosages were incubated at 37 degrees C with the microsomal metabolic system in vitro respectively. The supernatants were incubated with 1% RBC suspension. The OD635nm values of the supernatants were detected after incubation and centrifugation. The results showed that both primaquine and M 8506 exhibited potent hemolytic toxicity at the dose-range of 1.5-3 x (10(1)-10(3) mumol/L, with certain dose-effect relationship, while chloroquine exhibited no hemolytic toxicity. It is suggested that the in vitro assay incorporated with microsomal metabolic system might be a useful preliminary screening method for testing hemolytic toxicity of various antimalarials.
体外代谢系统由烟酰胺腺嘌呤二核苷酸磷酸（NADP）辅助因子和从经腹腔注射60 mg/kg苯巴比妥预处理3天并单次腹腔注射80 mg/kg萘黄酮的雄性大鼠分离得到的肝微粒体组成。1%红细胞悬液由葡萄糖-6-磷酸脱氢酶（G6PD）缺乏的兔血制备。分别将不同剂量的伯氨喹、氯喹和M 8506在37℃下与体外微粒体代谢系统孵育。将上清液与1%红细胞悬液孵育。孵育和离心后检测上清液的OD635nm值。结果显示，在1.5 - 3×（10¹ - 10³）μmol/L剂量范围内，伯氨喹和M 8506均表现出较强的溶血毒性，具有一定的剂量效应关系，而氯喹未表现出溶血毒性。提示结合微粒体代谢系统的体外试验可能是检测各种抗疟药溶血毒性的一种有用的初步筛选方法。
