An in vitro model for screening antileishmanial drugs: the human leukaemia monocyte cell line, THP-1.
Standard anti-leishmanial drugs were tested for their ability to inhibit the growth of intracellular amastigotes of Leishmania aethiopica, L. donovani and L. infantum in the human leukemia monocyte THP-1 cell line. Sodium stibogluconate and meglumine antimoniate were active against L. donovani with ED50 values of 8.9 micrograms SbV/ml and 2.9 micrograms SbV/ml, respectively. L. aethiopica was less sensitive to sodium stibogluconate with an ED50 value of 25.3 micrograms SbV/ml while pentamidine had an ED50 value of 0.6 microM. Both L. donovani (ED50, 9.3 microM), and L. aethiopica (ED50, 6.4 microM), were sensitive to aminosidine sulphate. An L. infantum isolate, clinically resistant to meglumine antimoniate treatment, had an ED50 of 22.2 micrograms SbV/ml. The toxic level of drugs on host cells was determined by colorimetric Methyl Tetrazolium (MTT) assay prior to activity tests. The results obtained with the THP-1 in vitro drug screening model were similar to those obtained in the mouse peritoneal macrophage model.
Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
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Gebre-Hiwot
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Tadesse
S L
SL
Croft
D
D
Frommel
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D007948:Leukemia, Monocytic, Acute; D008536:Meglumine / Q000494:pharmacology; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000494:pharmacology; D010303:Paromomycin; D010419:Pentamidine / Q000494:pharmacology; D013045:Species Specificity; D014407:Tumor Cells, Cultured
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010303:Paromomycin; D010419:Pentamidine; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000967:Antimony Sodium Gluconate