In-Vitro Toxicity Assessment of Antimalarial Drugs on Cultured Embryonic Rat Neurons, Macrophage (RAW 264.7), and Kidney Cells (VERO-CC1-81)
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Malaria is endemic to 106nations 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 in vivo 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. In previous studies, mefloquine has been proven to be highly neurotoxic resulting in adverse effects such as central nervous system damage, hallucinations, depression, paranoia and suicidal ideation. Although in-vitro toxicity assays have been conducted for numerous antimalarial drugs separately, relative composite studies have not been thoroughly explored. This study was performed to compare the relative toxic levels of eight antimalarial drugs to mefloquine in the rat macrophage (RAW 264.7), African green monkey kidney (VEROCC1- 81), and neuronal cell lines. For each drug, neurotoxicity was assessed by exposure of cultured embryonic rat neurons to varied concentrations of the drugs and activity was measured using a photo spectrophotometer to obtain the absorbance. Mefloquine exhibited the highest level of neurotoxicity in relation to all other antimalarial drugs with the exception of Tafenoquine as indicated by IC50 values. A general toxicity assay was also conducted to Compare the effects of the antimalarial drugs in a rat macrophage and African green monkey kidney cell line, which were exposed to varied concentrations of the drugs for a 24 hour incubation period. The general toxicity results indicated that mefloquine exhibited the highest degree of toxicity when compared to all eight antimalarial drugs as indicated by IC50 values. Collectively these data suggest that the profile of toxicity was significantly analogous in all three cell lines investigated. It can be concluded that mefloquine is significantly more toxic in the RAW, VERO and neuronal cell lines than the eight antimalarial drugs investigated.