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Menadione kills trophozoites and cysts of Giardia intestinalis

Paget, Timothy, Maroulis, Sarah, Mitchell, Andrew, Edwards, Michael R, Jarroll, Edward L and Lloyd, David 2004. Menadione kills trophozoites and cysts of Giardia intestinalis. Microbiology 150 (5) , 1231--1236. 10.1099/mic.0.26836-0

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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 Giardia intestinalis 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 O2. Under microaerobic conditions, similar to those on the surface of the jejunal mucosa, trophozoites consumed O2 rapidly in the presence of menadione; reaction products included singlet O2 (monitored by single photon counting of O2-dependent low-level chemiluminescence) and H2O2 (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 LC50 values (μg ml−1) of 1·2 and 0·7, respectively; corresponding values for cysts (measured by in vitro excystation capacities) were >50 and 1·3. Menadione (LD50 in mice, 0·5 g kg−1) is therefore a potentially more useful and general anti-giardial agent than metronidazole, as it is active against cysts as well as trophozoites.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Microbiology Society
ISSN: 1350-0872
Date of Acceptance: 5 February 2004
Last Modified: 24 Feb 2020 15:30
URI: http://orca.cf.ac.uk/id/eprint/128001

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