Experimental meningitis in the rat: protection by uric acid at human physiological blood concentrations

The natural peroxynitrite scavenger uric acid was previously shown to be protective in a rat model of pneumococcal meningitis however, rats have much lower blood uric acid levels than humans. Therefore. we evaluated its therapeutic effect at human physiological blood concentrations. Intraperitoneal pretreatment with uric acid increased its blood concentrations from 44.9 +/- 10.0 muM in untreated rats to 169.8 +/- 122.6 muM and reduced the cerebrospinal fluid (CSF) pleocytosis from 12 767 +/- 2520 to 8376 +/- 2450 cells/mul (P < 0.05) and the intracranial pressure from 11.6 +/- 3.0 to 4.3 +/- 1.2 mm Hg (P < 0.05). Coadministration of oxonic acid, an inhibitor of urate oxidase, increased the blood uric acid levels to 355.0 +/- 79.6 LM and further reduced the CSF pleocytosis (4190 +/- 1749 cells/mul, P < 0.05) and the intracranial pressure (1.4 +/- 2.4 mm Hg). Uric acid + oxonic acid also had a beneficial effect when adminstered 2 or 4 h after the induction of meningitis. We demonstrate a dose-dependent anti-inflammatory effect of uric acid at blood levels in the human physiological range. (C) 2001 Elsevier Science B.V. All rights reserved.