Reduced synthesis of inflammatory cytokines by a free radical scavenger after hemorrhagic shock in rats.
OBJECTIVE
Intestinal ischemia/reperfusion during hemorrhage and resuscitation may be a major trigger for cytokine expression. To assess whether free radicals produced on tissue reperfusion may play a role in the inflammatory response after hemorrhage, we tested the effect of a free radical scavenger on the production of inflammatory cytokines in a rat model of hemorrhagic shock.


METHODS
A prospective, controlled animal study.


METHODS
A university research laboratory.


METHODS
Male Wistar rats.


METHODS
Hemorrhage was induced in anesthetized rats. by bleeding the animal to achieve a mean arterial blood pressure of 40 mm Hg for 60 mins. Resuscitation was then induced by reinjecting shed blood followed by NaCl 0.9% to maintain arterial blood pressure within control values. Treated rats received the free radical scavenger N-2-mercaptopropionyl glycine (MPG; 20mg/kg iv bolus 30 mins before resuscitation followed by 20 mg/kg/hr).


RESULTS
MPG reduced the volume of saline necessary to restore blood pressure during resuscitation (untreated 85+/-6; MPG 35+/-5 mL/kg; p < .05). As compared with untreated rats, MPG markedly reduced the systemic and mesenteric plasma concentrations of tumor necrosis factor (TNF)-alpha (as measured by ELISA) and interleukin (IL)-6 (as measured by bioassay), assessed at the end of resuscitation. MPG also reduced TNF-alpha and IL-6 mRNA expression (as measured by reverse transcriptase-polymerase chain reaction) assessed in peritoneal macrophages isolated from shock rats. Finally, in vitro experiments showed that MPG also markedly reduced the mRNA expression and release of TNF-alpha and IL-6 in peritoneal macrophages isolated from normal rats and subjected to hypoxia and reoxygenation.


CONCLUSIONS
Reactive oxygen species contribute to the production of proinflammatory cytokines during posthemorrhage resuscitation. Free radicals scavengers may be a useful treatment in the prevention of the systemic inflammatory response that occurs in shock states.
Tamion
F
F
IFRMP 23, INSERM E9920, Rouen University Hospital, France.
Richard
V
V
Bonmarchand
G
G
Leroy
J
J
Hiron
M
M
Daveau
M
M
Thuillez
C
C
Lebreton
J P
JP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001804:Blood Transfusion, Autologous; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018075:RNA, Complementary / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000628:therapy; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000975:Antioxidants; D016166:Free Radical Scavengers; D015850:Interleukin-6; C110658:N-(2-mercaptoproprionyl)-glycine; D018075:RNA, Complementary; D013438:Sulfhydryl Compounds; D014409:Tumor Necrosis Factor-alpha; D005998:Glycine