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 pr otective in a rat model of pneumococcal meningitis however, rats have much lower blood uric acid levels than humans. Therefore. we evaluated its thera peutic 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 cerebro spinal 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 fur ther reduced the CSF pleocytosis (4190 +/- 1749 cells/mul, P < 0.05) and th e intracranial pressure (1.4 +/- 2.4 mm Hg). Uric acid + oxonic acid also h ad a beneficial effect when adminstered 2 or 4 h after the induction of men ingitis. We demonstrate a dose-dependent anti-inflammatory effect of uric a cid at blood levels in the human physiological range. (C) 2001 Elsevier Sci ence B.V. All rights reserved.