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Open AccessArticle

Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis

1
Children’s Hospital, Helsinki University Hospital, Stenbäckinkatu 9, 00029 Helsinki, Finland
2
Faculty of Medicine, University of Helsinki, Yliopistonkatu 4, 00014 Helsinki, Finland
3
Faculty of Medicine, University Diego Portales, Manuel Rodrigues Sur 333, 8370109 Santiago Region Metropolitana, Chile
4
Health Research Institute La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain
5
Hospital Pediátrico David Bernardino, Rua Amilcar Cabral, Luanda, Angola
6
Division of Neonatology, University and Polytechnic Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(10), 441; https://doi.org/10.3390/antiox8100441
Received: 29 August 2019 / Revised: 21 September 2019 / Accepted: 24 September 2019 / Published: 1 October 2019
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
The immunological response in bacterial meningitis (BM) causes the formation of reactive oxygen and nitrogen species (ROS, RNS) and activates myeloperoxidase (MPO), an inflammatory enzyme. Thus, structural oxidative and nitrosative damage to proteins and DNA occurs. We aimed to asses these events in the cerebrospinal fluid (CSF) of pediatric BM patients. Phenylalanine (Phe), para-tyrosine (p-Tyr), nucleoside 2′-deoxiguanosine (2dG), and biomarkers of ROS/RNS-induced protein and DNA oxidation: ortho-tyrosine (o-Tyr), 3-chlorotyrosine (3Cl-Tyr), 3-nitrotyrosine (3NO₂-Tyr) and 8-oxo-2′-deoxyguanosine (8OHdG), concentrations were measured by liquid chromatography coupled to tandem mass spectrometry in the initial CSF of 79 children with BM and 10 without BM. All biomarkers, normalized with their corresponding precursors, showed higher median concentrations (p < 0.0001) in BM compared with controls, except 8OHdG/2dG. The ratios o-Tyr/Phe, 3Cl-Tyr/p-Tyr and 3NO₂-Tyr/p-Tyr were 570, 20 and 4.5 times as high, respectively. A significantly higher 3Cl-Tyr/p-Tyr ratio was found in BM caused by Streptococcus pneumoniae, than by Haemophilus influenzae type b, or Neisseria meningitidis (p = 0.002 for both). In conclusion, biomarkers indicating oxidative damage to proteins distinguished BM patients from non-BM, most clearly the o-Tyr/Phe ratio. The high 3Cl-Tyr/p-Tyr ratio in pneumococcal meningitis suggests robust inflammation because 3Cl-Tyr is a marker of MPO activation and, indirectly, of inflammation. View Full-Text
Keywords: oxidative stress; protein damage; myeloperoxidase; bacterial meningitis; developing countries oxidative stress; protein damage; myeloperoxidase; bacterial meningitis; developing countries
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MDPI and ACS Style

Rugemalira, E.; Roine, I.; Kuligowski, J.; Sánchez-Illana, Á.; Piñeiro-Ramos, J.D.; Andersson, S.; Peltola, H.; Leite Cruzeiro, M.; Pelkonen, T.; Vento, M. Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis. Antioxidants 2019, 8, 441.

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