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Antioxidants (Basel). 2019 Oct 1;8(10). pii: E441. doi: 10.3390/antiox8100441.

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

Author information

1
Children's Hospital, Helsinki University Hospital, Stenbäckinkatu 9, 00029 Helsinki, Finland. emilie.rugemalira@helsinki.fi.
2
Faculty of Medicine, University of Helsinki, Yliopistonkatu 4, 00014 Helsinki, Finland. emilie.rugemalira@helsinki.fi.
3
Faculty of Medicine, University Diego Portales, Manuel Rodrigues Sur 333, 8370109 Santiago Region Metropolitana, Chile. irmeli.roine@gmail.com.
4
Health Research Institute La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain. julia.kuligowski@uv.es.
5
Health Research Institute La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain. asanchezillana@gmail.com.
6
Health Research Institute La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain. josedavidpineiro@gmail.com.
7
Children's Hospital, Helsinki University Hospital, Stenbäckinkatu 9, 00029 Helsinki, Finland. sture.andersson@helsinki.fi.
8
Faculty of Medicine, University of Helsinki, Yliopistonkatu 4, 00014 Helsinki, Finland. sture.andersson@helsinki.fi.
9
Children's Hospital, Helsinki University Hospital, Stenbäckinkatu 9, 00029 Helsinki, Finland. heiheikkipeltola@gmail.com.
10
Faculty of Medicine, University of Helsinki, Yliopistonkatu 4, 00014 Helsinki, Finland. heiheikkipeltola@gmail.com.
11
Hospital Pediátrico David Bernardino, Rua Amilcar Cabral, Luanda, Angola. mcruzeiro1@gmail.com.
12
Children's Hospital, Helsinki University Hospital, Stenbäckinkatu 9, 00029 Helsinki, Finland. tuula.pelkonen@hotmail.com.
13
Faculty of Medicine, University of Helsinki, Yliopistonkatu 4, 00014 Helsinki, Finland. tuula.pelkonen@hotmail.com.
14
Hospital Pediátrico David Bernardino, Rua Amilcar Cabral, Luanda, Angola. tuula.pelkonen@hotmail.com.
15
Health Research Institute La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain. maximo.vento@uv.es.
16
Division of Neonatology, University and Polytechnic Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain. maximo.vento@uv.es.

Abstract

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.

KEYWORDS:

bacterial meningitis; developing countries; myeloperoxidase; oxidative stress; protein damage

PMID:
31581487
DOI:
10.3390/antiox8100441
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