Paget, T.A. and Maroulis, S. and Mitchell, A. and Edwards, M.R. and Jarroll, E.L. and Lloyd, D. (2004) Menadione kills trophozoltes and cysts of Giardia intestinalis. Microbiology-SGM , 150 (5). pp. 1231-1236. ISSN 1350-0872.
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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:||14 Jan 2010 14:29|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/8102 (The current URI for this page, for reference purposes)|
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