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Are reactive oxygen species involved in the pathogenesis of murine cerebral malaria?
1Department of Pathology, Heart Research Institute, University of Sydney, Australia.
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.
Insights
Oxidative tissue damage does not appear to play a role in murine cerebral malaria (CM). Studies found no significant differences in oxidative markers or disease course in knockout mice, suggesting reactive oxygen species are not involved in CM pathogenesis.
Area of Science:
- Pathology
- Immunology
- Neuroscience
Background:
- Cerebral malaria (CM) pathogenesis is complex.
- The role of oxidative stress in CM remains unclear.
Purpose of the Study:
- To investigate the involvement of oxidative tissue damage in murine cerebral malaria (CM).
- To determine if reactive oxygen species contribute to CM pathogenesis.
Main Methods:
- Measured brain levels of oxidative stress markers (protein carbonyls, DOPA, o-tyrosine, dityrosine) in Plasmodium berghei ANKA (PbA) infected mice.
- Examined CM course in gp91phox gene knockout mice lacking phagocyte NADPH oxidase.
- Assessed xanthine oxidase activity via brain urate concentrations in CM and non-CM models.
Main Results:
- Brain oxidative stress markers were similar between CM and uninfected mice.
- gp91phox knockout mice exhibited a similar CM course to wild-type controls.
- Increased brain urate levels in both CM and non-CM groups indicated non-specific purine breakdown.
Conclusions:
- Reactive oxygen species likely do not contribute to the pathogenesis of murine CM.
- Oxidative tissue damage is probably not a key factor in CM development.