Mercaptoethylguanidine attenuates inflammation in bacterial meningitis in rabbits.
Reactive oxygen and nitrogen species participate in the inflammatory process during meningitis. Among them, superoxide, nitric oxide (NO), and their reaction product peroxynitrite exert cytotoxic effects. Mercaptoethylguanidine (MEG) exerts beneficial effects in in vivo inflammatory conditions by scavenging peroxynitrite and inhibiting the inducible NO synthase. This study was designed to investigate whether MEG may attenuate inflammation and brain injury in experimental meningitis. Meningitis increased nitrite/nitrate, and protein content in the cerebrospinal fluid (CSF). In the brain tissue high levels of malondialdehyde and formation of nitrotyrosine indicated lipid peroxidation and nitrosative stress, respectively. Myeloperoxidase activity was increased indicating accumulation of neutrophils into the brain parenchyma. Treatment with MEG decreased nitrite/nitrate levels whereas it did not affect the bacterial clearance from the CSF. Furthermore, treatment with MEG markedly reduced brain tissue levels of myeloperoxidase and malondialdehyde. These data demonstrate that MEG could have a therapeutic role in meningitis.
Irazuzta
J E
JE
Division of Critical Care, Children's Hospital Medical Center, Cincinnati, OH, USA. Irazuzta@aol.com
Mirkin
L D
LD
Zingarelli
B
B
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology; D008585:Meningitis, Meningococcal; D009566:Nitrates / Q000134:cerebrospinal fluid; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000134:cerebrospinal fluid; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D011817:Rabbits; D013290:Streptococcal Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology; D013292:Streptococcus agalactiae; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D011506:Proteins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D009195:Peroxidase; D019001:Nitric Oxide Synthase; C100078:2-mercaptoethylguanidine