Development of a pharmacodynamic screening model with Entamoeba histolytica.
Human amoebiasis caused by Entamoeba histolytica is widely distributed in the tropics and subtropics, but also occurring in neighbouring parts of the temperate zones. Invasive amoebiasis causes dysentery and, by haematogenous spread, also extra-intestinal hepatic, pulmonary or cerebral abscesses, not rarely fatal conditions. The available anti-amoebic drugs have shortcomings regarding tolerability and efficacy. To facilitate the screening of candidate material, an in vitro system has been developed that permits the determination of specific anti-amoebic activity. PYE medium, supplemented with bovine serum, proved to be suitable for the maintenance of the stock cultures of Entamoeba histolytica strain HM1:1MSS. For sensitivity testing, Waymouth medium and cultivation under aerobic conditions were most reliable. After adapting the system to the use of 96-well (8 x 12) tissue culture plates, sensitivity tests were carried out with metronidazole, dehydroemetine and dihydroartemisinin as active control drugs, and seven extracts from Stemona tuberosa, Aglaia edulis, Aglaia elaeagnoidea and Aglaia odorata. Stem bark extract from Aglaia elaeagnoidea was the most active material with an IC(99) of 496 ng/ml and a slope S of 1.1325, followed by leaf extract from Stemona tuberosa with an IC(99) of 638 ng/ml and a slope S of 1.5648. All seven extracts showed full activity at concentrations <4000 ng/ml and qualified for further investigation.
Tasanor
Oumaporn
O
Institute for Specific Prophylaxis und Tropical Medicine, Center for Physiology und Pathophysiology, Medical University of Vienna, Vienna, Austria. tasanor@yahoo.com
Brem
Brigitte
B
Leitsch
David
D
Binder
Marina
M
Duchêne
Michael
M
Greger
Harald
H
Wernsdorfer
Walther H
WH
D000962:Antimalarials / Q000008:administration & dosage* / Q000145:classification*; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001681:Biological Assay / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000378:metabolism*; D015996:Survival Rate
D000962:Antimalarials; D000981:Antiprotozoal Agents