[In vitro assay for detecting hemolytic toxicity of antimalarials incorporated with microsomal metabolic system].
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.
Ni
Y C
YC
Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine.
Xu
Y Q
YQ
D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D002738:Chloroquine / Q000633:toxicity; D006461:Hemolysis; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D011319:Primaquine / Q000633:toxicity / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains
D000634:Aminoquinolines; D000962:Antimalarials; D002738:Chloroquine; C069677:M 8506; D011319:Primaquine