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In‐Vitro Toxicity Assessment of Antimalarial Drug Toxicity on Cultured Embryonic Rat Neurons, Macrophage (RAW 264.7), and Kidney Cells (VERO‐CCl‐81)
Author(s) -
Agboruche Rebecca Latice
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.529.3
Subject(s) - mefloquine , toxicity , pharmacology , neurotoxicity , population , malaria , drug , adverse effect , plasmodium falciparum , medicine , biology , toxicology , immunology , environmental health
Malaria is endemic to 106 nations and currently threatens over half of the world's population. Today it is becoming increasingly important to find effective antimalarial drugs with substantial half‐lives and few adverse effects. In the United States, Mefloquine remains the primary drug of choice for U.S. military deployments and civilians traveling to regions where malaria is prevalent. However, in previous studies, mefloquine has been proven to be highly neurotoxic contributing to numerous adverse effects. Throughout this study, the 50% inhibitory concentration (IC 50 ) of eight antimalarial drugs will be compared to mefloquine in an attempt to compare their relative toxicity levels. For each drug, neurotoxicity was assessed by exposure of cultured embryonic rat neurons to graded concentrations of the drugs for 20 min. Mefloquine exhibited the highest level of neurotoxicity in relation to all other antimalarial drugs with the exception of Tafenoquine as indicated by the IC 50 values. A general toxicity assay was also conducted to compare the effects of the antimalarial drugs in a rat macrophage (RAW 264.7) and African green monkey kidney (VERO‐CCl‐81) cell line. The general toxicity results indicated that mefloquine exhibited the highest degree of toxicity when compared to all eight antimalarial drugs as indicated by IC 50 values. Collectively these data suggest that the profile of toxicity was analogous in all three cell lines investigated. The growing prevalence of malaria calls for antimalarial drugs which are highly effective and don't contribute to adverse side effects. This investigation demonstrates that mefloquine is considerably more toxic than all eight antimalarial drugs analyzed within the study. Therefore it is highly plausible that alternative antimalarial drugs with negligible degrees of toxicity can be administered as a substitute for mefloquine.