A POSSIBLE MECHANISM OF ELLIPTICINE-INDUCED HEMOLYSIS

摘要: Ellipticine (E) [5,11-dimethyl-6H-pyrido-(4,3-b)-carbazole, NSC-71795] is an antineoplastic agent which active against L1210 lymphocytic leukemia in mice. Preclinical toxicologic studies demonstrated hemolysis dogs and monkeys following intravenous administration of 1.5 mg/kg. This finding prompted this investigation the mechanism a study various factors that might ameliorate effect. Initial experiments human red blood cells were completely hemolyzed at E concentration 10-3 M, while 10-4 M stabilized 150 mOsM NaCl. The extent correlated well with surface activities, lipophilic properties cellular uptake some its derivatives (7,10-dimethylellipticine, isoellipticine, 9-methoxyellipticine 11-demethylellipticine). greatest occurred 7,10-dimethylellipticine least 11-demethylellipticine. was linear over wide range not temperature-dependent. Hemolysis could be blocked by citrate, sodium ethylenediamine tetraacetate, oxytetracycline [(±)-1,2-bis(3,5-dioxopiperazin-1-y1)propane]. inhibition citrate appears to noncompetitive process has Ki 1.9 x M. These data suggest Ca++ involved hemolytic E. ellipticine rhesus monkey caused severe prevented simultaneous injection citrate.