Document Detail

Experimental meningitis in the rat: protection by uric acid at human physiological blood concentrations.
MedLine Citation:
PMID:  11502281     Owner:  NLM     Status:  MEDLINE    
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 microM in untreated rats to 169.8+/-122.6 microM and reduced the cerebrospinal fluid (CSF) pleocytosis from 12767+/-2520 to 8376+/-2450 cells/microl (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 microM and further reduced the CSF pleocytosis (4190+/-1749 cells/microl, P<0.05) and the intracranial pressure (1.4+/-2.4 mm Hg). Uric acid+oxonic acid also had a beneficial effect when administered 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.
S Kastenbauer; U Koedel; B F Becker; H W Pfister
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  425     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-14     Completed Date:  2001-09-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  149-52     Citation Subset:  IM    
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich, Germany.
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MeSH Terms
Disease Models, Animal
Meningitis, Pneumococcal / blood,  cerebrospinal fluid,  prevention & control*
Protective Agents / therapeutic use*
Rats, Wistar
Uric Acid / blood,  cerebrospinal fluid,  therapeutic use*
Reg. No./Substance:
0/Protective Agents; 69-93-2/Uric Acid

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