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- W1987842432 abstract "Malaria is a crucial problem in public health care, affecting 200 million people annually, two million of whom die. Chloroquine resistance has become widespread and alternative agents including quinoline derivatives, pyrimethamine and qinghaosu derivatives are used now in malaria treatment. These compounds were comparatively studied for their cytotoxicity and CYP induction capability in rat hepatocyte primary cultures. Chloroquine, mefloquine, amodiaquine and arteflene had IC50s of approximately 40 μm, whereas quinidine, primaquine, quinine and pyrimethamine were less toxic (IC50s of approx. 300 μm). CYP induction was also tested by using PROD, ECOD and EROD activities as markers. Primaquine, pyrimethamine, quinine, mefloquine and chloroquine provoked an approximately 1.5-fold induction of PROD activity over control. Concerning ECOD activity, amodiaquine and pyrimethamine led to a approximately 5.1- and 2.5-fold increases, respectively, whereas a 12-fold induction was obtained with primaquine. EROD activity was only induced by primaquine (approx. eightfold). This induction was dose dependent and correlated to a rise in CYP1A1 mRNA level. Finally, induction by primaquine appeared to be mediated via the Ah receptor, as indicated by its suppression by 8-MP, a compound interfering with the binding of activated AhR to DNA. These findings may have pharmacotoxicological implications and should be considered in the design of therapeutic protocols." @default.
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- W1987842432 date "1998-10-01" @default.
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- W1987842432 title "Cytochrome P450 Induction and Cytotoxic effects of Antimalarials in Rat Hepatocytes" @default.
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- W1987842432 doi "https://doi.org/10.1016/s0887-2333(98)00033-2" @default.
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