| Abstract: | The effect of nitroxynil, rafoxanide, diamphenethide, oxyclozanide and hexachlorophene on the malate dehydrogenase activity of homogenates of Fasciola hepatica was investigated. The ratio of oxaloacetate reduction to malate oxidation in homogenates of F. hepatica was 6.2:1. Nitroxynil, rafoxanide and diamphenethide had no inhibitory effect on malate dehydrogenase at 10?3 M . Oxyclozanide at 10?3 M inhibited malate oxidation by 100% and oxaloacetate reduction by 81%, while 10?3 M hexachlorophene inhibited activity in both directions by 100%. The inhibition quotient (K1 of bovine liver/Ki of F. hepatica) was 7.8 for oxyclozanide and 5.4 for hexachlorophene. No inhibition was seen with 2,4-dinitrophenol at 10?3 M . Rapid death resulted in vitro with 10?4 M oxyclozanide and 10?5 M hexachlorophene. Oxaloacetate reduction was inhibited 61% and malate oxidation 91% with oxyclozanide and 71 and 100% respectively with hexachlorophene. Slow death was also seen at 10?6 M concentration with both products although there was only 30% inhibition of malate dehydrogenase. Both products act as non-competitive inhibitors of malate dehydrogenase and this inhibition is more marked against the mitochondrial subcellular fraction than the cytoplasmic fraction. |
