Paget, Timothy A. and Maroulis, Sarah and Mitchell, Andrew and Edwards, Michael R. and Jarroll, Edward L. and Lloyd, David (2004) Menadione kills trophozoltes and cysts of Giardia intestinalis. Microbiology, 150 (5). pp. 1231-1236. ISSN 0002-4564. (The full text of this publication is not available from this repository)
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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 O-2. Under microaerobic conditions, similar to those on the surface of the jejunal mucosa, trophozoites consumed O-2 rapidly in the presence of menadione; reaction products included singlet O-2 (monitored by single photon counting of O-2-dependent low-level chemiluminescence) and H2O2 (measured by the formation of Complex I of microperoxiclase). 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 metroniclazole and menadione gave LC50 values (pg 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.
|Divisions:||Faculties > Science Technology and Medical Studies > Medway School of Pharmacy|
|Depositing User:||Tim Paget|
|Date Deposited:||26 Sep 2008 15:14|
|Last Modified:||30 Apr 2014 10:59|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/8102 (The current URI for this page, for reference purposes)|
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