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Multivariate modelling with (1)H NMR of pleural effusion in murine cerebral malaria
Soumita Ghosh1, Arjun Sengupta, Shobhona Sharma
1Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India.
Background:
Cerebral malaria is a clinical manifestation of Plasmodium falciparum infection. Although brain damage is the predominant pathophysiological complication of cerebral malaria (CM), respiratory distress, acute lung injury, hydrothorax/pleural effusion are also observed in several cases. Immunological parameters have been assessed in pleural fluid in murine models; however there are no reports of characterization of metabolites present in pleural effusion.
Methods:
1H NMR of the sera and the pleural effusion of cerebral malaria infected mice were analyzed using principal component analysis, orthogonal partial least square analysis, multiway principal component analysis, and multivariate curve resolution.
Results:
It has been observed that there was 100% occurrence of pleural effusion (PE) in the mice affected with CM, as opposed to those are non-cerebral and succumbing to hyperparasitaemia (NCM/HP). An analysis of 1H NMR and SDS-PAGE profile of PE and serum samples of each of the CM mice exhibited a similar profile in terms of constituents. Multivariate analysis on these two classes of biofluids was performed and significant differences were detected in concentrations of metabolites. Glucose, creatine and glutamine contents were high in the PE and lipids being high in the sera. Multivariate curve resolution between sera and pleural effusion showed that changes in PE co-varied with that of serum in CM mice. The increase of glucose in PE is negatively correlated to the glucose in serum in CM as obtained from the result of multiway principal component analysis.
Conclusions:
This study reports for the first time, the characterization of metabolites in pleural effusion formed during murine cerebral malaria. The study indicates that the origin of PE metabolites in murine CM may be the serum. The loss of the components like glucose, glutamine and creatine into the PE may worsen the situation of patients, in conjunction with the enhanced glycolysis, glutaminolysis and increased activity of creatine phophokinase which are already reported characteristic pathophysiological features of malaria.
Insights
Pleural effusion in cerebral malaria (CM) mice contains metabolites originating from serum. This metabolite shift, including high glucose and creatine in effusion, may worsen CM patient outcomes.
Area of Science:
- Metabolomics
- Biochemistry
- Pathophysiology
Background:
- Cerebral malaria (CM) is a severe Plasmodium falciparum infection.
- While brain damage is primary, respiratory complications like pleural effusion occur.
- Metabolite analysis of pleural effusion in CM is previously unreported.
Purpose of the Study:
- To characterize metabolites in pleural effusion during murine CM.
- To investigate the origin of these pleural effusion metabolites.
- To understand potential implications for CM pathophysiology.
Main Methods:
- 1H NMR spectroscopy of serum and pleural effusion in CM mice.
- Multivariate statistical analyses (PCA, OPLS-DA, MCR).
- SDS-PAGE for constituent profiling.
Main Results:
- 100% occurrence of pleural effusion in CM mice.
- Similar constituent profiles but different metabolite concentrations between serum and effusion.
- Elevated glucose, creatine, and glutamine in pleural effusion; elevated lipids in serum.
- Pleural effusion metabolite changes correlated with serum changes, with inverse glucose correlation.
Conclusions:
- First characterization of pleural effusion metabolites in murine CM.
- Evidence suggests serum as the origin of pleural effusion metabolites.
- Loss of glucose, glutamine, and creatine into effusion may exacerbate CM by impacting glycolysis and related pathways.
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