Marked elevation in cortical urate and xanthine oxidoreductase activity in experimental bacterial meningitis.
Experimental bacterial meningitis due to Streptococcus pneumoniae in infant rats was associated with a time-dependent increase in CSF and cortical urate that was approximately 30-fold elevated at 22 h after infection compared to baseline. This increase was mirrored by a 20-fold rise in cortical xanthine oxidoreductase activity. The relative proportion of the oxidant-producing xanthine oxidase to total activity did not increase, however. Blood plasma levels of urate also increased during infection, but part of this was as a consequence of dehydration, as reflected by elevated ascorbate concentrations in the plasma. Administration of the radical scavenger alpha-phenyl-tert-butyl nitrone, previously shown to be neuroprotective in the present model, did not significantly affect either xanthine dehydrogenase or xanthine oxidase activity, and increased even further cortical accumulation of urate. Treatment with the xanthine oxidoreductase inhibitor allopurinol inhibited CSF urate levels earlier than those in blood plasma, supporting the notion that urate was produced within the brain. However, this treatment did not prevent the loss of ascorbate and reduced glutathione in the cortex and CSF. Together with data from the literature, the results strongly suggest that xanthine oxidase is not a major cause of oxidative stress in bacterial meningitis and that urate formation due to induction of xanthine oxidoreductase in the brain may in fact represent a protective response.
Christen
S
S
Institute for Infectious Diseases, University of Berne, Friedbühlstrasse 51, CH-3010, Berne, Switzerland. stephan.christen@imm.unibe.ch
Bifrare
Y D
YD
Siegenthaler
C
C
Leib
S L
SL
Täuber
M G
MG
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D008586:Meningitis, Pneumococcal / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014527:Uric Acid / Q000134:cerebrospinal fluid / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D014527:Uric Acid; C029217:phenyl-N-tert-butylnitrone; D000493:Allopurinol; D010088:Oxidoreductases; D014969:Xanthine Oxidase