A free radical scavenger, edaravone (MCI-186), diminishes intestinal neutrophil lipid peroxidation and bacterial translocation in a rat hemorrhagic shock model.
OBJECTIVE
To investigate the effects of edaravone, a novel free radical scavenger, on bacterial translocation induced by hemorrhagic shock.


METHODS
Prospective, randomized, unblinded animal study.


METHODS
Surgical research laboratories of Shiga University of Medical Science.


METHODS
Male specific-pathogen-free Sprague-Dawley rats.


METHODS
The rats were randomly divided into three groups: conventional saline treatment, edaravone treatment, and sham shock induction. The saline and edaravone groups were subjected to hemorrhagic shock (mean arterial pressure of 30 mm Hg, for 30 or 60 mins). Rats were killed 30 or 60 mins after shock induction. Mesenteric lymph nodes were cultured for determination of bacterial translocation. Systemic plasma silkworm larvae plasma test, which can detect peptidoglycan and beta-glucan, and endotoxin tests were performed. Immunohistochemistry for 4-hydroxy-2-nonenal (4-HNE) was used to assess lipid peroxidation after shock.


RESULTS
The incidence and magnitude of hemorrhagic-shock-induced bacterial translocation to mesenteric lymph nodes were reduced by edaravone. Hemorrhagic-shock-induced increase of plasma silkworm larvae plasma test was also reduced by edaravone. Immunohistochemistry for 4-HNE showed many 4-HNE-positive cells in the lamina propria of the ileum 60 mins after hemorrhagic shock. Double immunohistochemistry revealed that many of these 4-HNE-positive cells were also myeloperoxidase positive. Moreover, the percentage of double-labeled cells with 4-HNE and myeloperoxidase in myeloperoxidase-positive cells was significantly lower in the edaravone group than in the saline group.


CONCLUSIONS
The present findings suggest that lipid peroxidation of intestinal neutrophils is involved in bacterial translocation during hemorrhagic shock and that edaravone is potentially useful in diminishing bacterial translocation after hemorrhagic shock.
Mori
Tsuyoshi
T
Department of Surgery, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu-shi Shiga, 520-2192 Japan.
Yamamoto
Hiroshi
H
Tabata
Takahisa
T
Shimizu
Tomoharu
T
Endo
Yoshihiro
Y
Hanasawa
Kazuyoshi
K
Fujimiya
Mineko
M
Tani
Tohru
T
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D018988:Bacterial Translocation / Q000187:drug effects* / Q000502:physiology; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D007082:Ileum / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008198:Lymph Nodes / Q000187:drug effects* / Q000382:microbiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine