title: Are reactive oxygen species involved in the pathogenesis of murine cerebral malaria?
abstract: To investigate the involvement of oxidative tissue damage in the pathogenesis of murine cerebral malaria (CM), brain levels of protein carbonyls, 3,4-dihydroxyphenylalanine (DOPA), o-tyrosine, and dityrosine were measured during Plasmodium berghei ANKA (PbA) and P. berghei K173 (PbK) infections. During PbA infection in a CM model, brain levels of the substances were similar to those in uninfected mice. The role of phagocyte-derived reactive oxygen species in the pathogenesis of CM was examined in gp91phox gene knockout mice. The course of CM in these mice was the same as in their wild type counterparts. To examine whether superoxide production in the central nervous system could have occurred via increased xanthine oxidase activity, brain concentrations of urate were measured in CM mice and in mice infected with PbK (which does not cause CM). Brain urate concentration increased significantly in both groups of mice, suggesting that purine breakdown is not specific to CM. These results indicate that reactive oxygen species probably do not contribute to the pathogenesis of murine CM.
authors.affiliation: Department of Pathology, Heart Research Institute, University of Sydney, Australia.
authors.forename: L A
authors.initials: LA
authors.lastname: Sanni
authors.forename: S
authors.initials: S
authors.lastname: Fu
authors.forename: R T
authors.initials: RT
authors.lastname: Dean
authors.forename: G
authors.initials: G
authors.lastname: Bloomfield
authors.forename: R
authors.initials: R
authors.lastname: Stocker
authors.forename: G
authors.initials: G
authors.lastname: Chaudhri
authors.forename: M C
authors.initials: MC
authors.lastname: Dinauer
authors.forename: N H
authors.initials: NH
authors.lastname: Hunt
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D016779:Malaria, Cerebral / Q000209:etiology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D010962:Plasmodium berghei; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D014527:Uric Acid; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; C026741:2-tyrosine; C007543:dityrosine; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases