Estrogen receptor hormone agonists limit trauma hemorrhage shock-induced gut and lung injury in rats.
BACKGROUND
Acute lung injury (ALI) and the development of the multiple organ dysfunction syndrome (MODS) is a major cause of death in trauma patients. Earlier studies in trauma hemorrhagic shock (T/HS) have documented that splanchnic ischemia leading to gut inflammation and loss of barrier function is an initial triggering event that leads to gut-induced ARDS and MODS. Since sex hormones have been shown to modulate the response to T/HS and proestrous (PE) females are more resistant to T/HS-induced gut and distant organ injury, the goal of our study was to determine the contribution of estrogen receptor (ER)alpha and ERbeta in modulating the protective response of female rats to T/HS-induced gut and lung injury.


RESULTS
The incidence of gut and lung injury was assessed in PE and ovariectomized (OVX) female rats subjected to T/HS or trauma sham shock (T/SS) as well as OVX rats that were administered estradiol (E2) or agonists for ERalpha or ERbeta immediately prior to resuscitation. Marked gut and lung injury was observed in OVX rats subjected to T/HS as compared to PE rats or E2-treated OVX rats subjected to T/HS. Both ERalpha and ERbeta agonists were equally effective in limiting T/HS-induced morphologic villous injury and bacterial translocation, whereas the ERbeta agonist was more effective than the ERalpha agonist in limiting T/HS-induced lung injury as determined by histology, Evan's blue lung permeability, bronchoalevolar fluid/plasma protein ratio and myeloperoxidase levels. Similarly, treatment with either E2 or the ERbeta agonist attenuated the induction of the intestinal iNOS response in OVX rats subjected to T/HS whereas the ERalpha agonist was only partially protective.


CONCLUSIONS
Our study demonstrates that estrogen attenuates T/HS-induced gut and lung injury and that its protective effects are mediated by the activation of ERalpha, ERbeta or both receptors.
Doucet
Danielle
D
Department of Surgery, University of Medicine & Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America.
Badami
Chirag
C
Palange
David
D
Bonitz
R Paul
RP
Lu
Qi
Q
Xu
Da-Zhong
DZ
Kannan
Kolenkode B
KB
Colorado
Iriana
I
Feinman
Rena
R
Deitch
Edwin A
EA
D000818:Animals; D020895:Enterocytes / Q000187:drug effects / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000502:physiology; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology; D030762:Estrous Cycle; D005260:Female; D007150:Immunohistochemistry; D007422:Intestines / Q000293:injuries; D055370:Lung Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D009102:Multiple Organ Failure / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications; D012774:Shock, Traumatic / Q000150:complications
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D004958:Estradiol; D052247:Nitric Oxide Synthase Type II