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

Antioxidants

Heikki Peltola¹  Sture Andersson¹  Emilie Rugemalira¹  Tuula Pelkonen¹  Irmeli Roine²  JoséDavid Piñeiro-Ramos³  Máximo Vento³  Julia Kuligowski³  Ángel Sánchez-Illana³  Manuel Leite Cruzeiro⁴ 

[1] Children’s Hospital, Helsinki University Hospital, Stenbäckinkatu 9, 00029 Helsinki, Finland;Faculty of Medicine, University Diego Portales, Manuel Rodrigues Sur 333, 8370109 Santiago Region Metropolitana, Chile;Health Research Institute La Fe, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain;Hospital Pediátrico David Bernardino, Rua Amilcar Cabral, Luanda, Angola;

关键词: oxidative stress;    protein damage;    myeloperoxidase;    bacterial meningitis;    developing countries;   

DOI  :  10.3390/antiox8100441

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown