3-nitrotyrosine and Meningitis--Bacterial

To study reactive nitrogen species-mediated oxidative brain damage and antioxidant defenses in patients with acute bacterial meningitis.. Nitrotyrosine (a widely used marker for the formation of reactive nitrogen species, such as peroxynitrite) and the lipid peroxidation product 4-hydroxynonenal were detected by immunohistochemistry in brain specimens obtained at autopsy. CSF concentrations of nitrotyrosine were quantified by ELISA. CSF and serum concentrations of ascorbic acid, uric acid, and its oxidation product allantoin were determined by high-pressure liquid chromatography.. Tyrosine nitration was strongly increased during meningitis. It was most evident in inflammatory cells and blood vessels in the subarachnoid space. The same cell types stained positive for the lipid peroxidation marker 4-hydroxynonenal, suggesting that reactive nitrogen species contribute to oxidative brain damage during meningitis. High CSF nitrotyrosine concentrations were associated with an unfavorable outcome according to the Glasgow Outcome Score. In the CSF, the increase of nitrotyrosine was accompanied by a depletion of the antioxidant ascorbic acid and an increased oxidation of the natural peroxynitrite scavenger uric acid to allantoin.. These findings indicate that oxidative stress due to reactive nitrogen species and altered antioxidant defenses are involved in the pathophysiology of bacterial meningitis in humans.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aldehydes; Allantoin; Ascorbic Acid; Brain; Cysteine Proteinase Inhibitors; Female; Free Radical Scavengers; Glasgow Outcome Scale; Humans; Immunohistochemistry; Male; Meningitis, Bacterial; Middle Aged; Neurons; Oxidative Stress; Reactive Nitrogen Species; Statistics as Topic; Treatment Outcome; Tyrosine; Uric Acid

Reactive oxygen and nitrogen species participate in the inflammatory process during meningitis. Among them, superoxide, nitric oxide (NO), and their reaction product peroxynitrite exert cytotoxic effects. Mercaptoethylguanidine (MEG) exerts beneficial effects in in vivo inflammatory conditions by scavenging peroxynitrite and inhibiting the inducible NO synthase. This study was designed to investigate whether MEG may attenuate inflammation and brain injury in experimental meningitis. Meningitis increased nitrite/nitrate, and protein content in the cerebrospinal fluid (CSF). In the brain tissue high levels of malondialdehyde and formation of nitrotyrosine indicated lipid peroxidation and nitrosative stress, respectively. Myeloperoxidase activity was increased indicating accumulation of neutrophils into the brain parenchyma. Treatment with MEG decreased nitrite/nitrate levels whereas it did not affect the bacterial clearance from the CSF. Furthermore, treatment with MEG markedly reduced brain tissue levels of myeloperoxidase and malondialdehyde. These data demonstrate that MEG could have a therapeutic role in meningitis.

Topics: Animals; Brain; Enzyme Inhibitors; Guanidines; Immunoenzyme Techniques; Male; Malondialdehyde; Meningitis, Bacterial; Meningitis, Meningococcal; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Peroxidase; Proteins; Rabbits; Streptococcal Infections; Streptococcus agalactiae; Tyrosine