In-vitro Additive Synergistic Anti-amoebic Effect of a Metronidazole—Gossypol Blend

Abstract

Gossypol has a potent anti-amoebic effect on both Entamoeba histolytica axenic cultures and experimental amoebic hepatic abscess. However, the margin between the in-vivo effective dose and the toxic dose in hamsters is relatively small. While metronidazole is widely used as an anti-amoebic medication, it is considered a possible carcinogen in man. With the aid of the Basic Sequential Analytical Simplex Method we tested the effectiveness of 12 metronidazole-gossypol blends where the concentration of each drug was systematically varied. Amoebic growth inhibition was observed (33–71% with respect to controls) using blends containing metronidazole (50–154 nM) and gossypol (5–16 nM). The combination containing metronidazole (88.61 nM) and gossypol (9.95 nM) caused 62% amoebic growth inhibition. These concentrations where 50% lower than those required to produce an equivalent effect using metronidazole or gossypol alone. Thus, the actions of metronidazole and gossypol against E. histolytica are additive. Accordingly, the in-vivo application of an appropriate combination of metronidazole and gossypol could be as effective as each drug alone, but less toxic to the host.