1887

Abstract

Production of reactive oxygen species by redox cycling in the presence of low levels of oxygen has been studied as a possible approach to anti-protozoal chemotherapeutic strategy. Incubation of the diplomonad flagellate with 2-methy-1,4-naphthoquinone (menadione), under anaerobic conditions, gave UV absorption changes characteristic of reduction to menadiol; partial reversal was observed on admitting O. Under microaerobic conditions, similar to those on the surface of the jejunal mucosa, trophozoites consumed O rapidly in the presence of menadione; reaction products included singlet O (monitored by single photon counting of O-dependent low-level chemiluminescence) and HO (measured by the formation of Complex I of microperoxidase). Trophozoites became swollen and incapable of regulatory volume control; these irreversible responses led to loss of motility, cessation of flagellar activity and cell death. Comparison of the sensitivities of trophozoites to metronidazole and menadione gave LC values (μg ml) of 1·2 and 0·7, respectively; corresponding values for cysts (measured by excystation capacities) were >50 and 1·3. Menadione (LD in mice, 0·5 g kg) is therefore a potentially more useful and general anti-giardial agent than metronidazole, as it is active against cysts as well as trophozoites.

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2004-05-01
2019-10-21
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