Effects of clinically used antioxidants in experimental pneumococcal meningitis.
Reactive oxygen intermediates mediate brain injury in bacterial meningitis. Several antioxidant drugs are clinically available, including N-acetylcysteine (NAC), deferoxamine (DFO), and trylizad-mesylate (TLM). The present study evaluated whether these antioxidants are beneficial in a model of pneumococcal meningitis. Eleven-day-old rats were infected intracisternally with Streptococcus pneumoniae and randomized to intraperitoneal treatment every 8 h with NAC (200 mg/kg), DFO (100 mg/kg), TLM (10 mg/kg), or saline (250 microL). TLM-treated animals showed a significantly reduced mortality compared with controls (P<.03). Meningitis led to extensive cortical injury at 22+/-2.2 h after infection (median, 14. 6% of cortex; range, 0-61.1%). Injury was significantly (P<.01) reduced to 1.1% (range, 0-34.6%) by NAC, to 2.3% (range, 0-19.6%) by DFO, and to 0.2% (range, 0-36.9%) by TLM (the difference was not significant among the 3 groups). None of the drugs reduced hippocampal injury. Thus, several clinically used antioxidants reduced cortical injury in experimental pneumococcal meningitis.
Auer
M
M
Institute for Medical Microbiology, Infectious Diseases Resaerch Laboratory, University of Bern, Bern, Switzerland. marc_auer@hotmail.com
Pfister
L A
LA
Leppert
D
D
Täuber
M G
MG
Leib
S L
SL
D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003676:Deferoxamine / Q000627:therapeutic use; D004195:Disease Models, Animal; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D003676:Deferoxamine; D000111:Acetylcysteine