Sex hormones modulate distant organ injury in both a trauma/hemorrhagic shock model and a burn model.
BACKGROUND
Emerging data suggest a gender dimorphism in resistance and susceptibility to distant organ injury after mechanical and thermal trauma. The aim of this study was to determine the role that testosterone and estradiol play in modulating resistance or susceptibility to distant organ injury, and whether their effects were associated with differences in the production of nitric oxide.


METHODS
Adult male, female, castrated male, and ovariectomized female Sprague-Dawley rats were given intraperitoneal pentobarbital sodium anesthesia and subjected to trauma/sham shock or trauma/hemorrhagic shock (T/HS). A second set of animals were subjected to a 40% total body surface area, third-degree burn or sham burn. At 3 hours after resuscitation, plasma levels of nitrite/nitrate were measured, and the extent of lung injury (permeability to Evans Blue dye and neutrophil sequestration by myeloperoxidase) and intestinal injury (morphology) were determined.


RESULTS
Proestrus females showed resistance to lung and gut injury after both T/HS and burns, and had low levels of nitrite/nitrate production. This resistance to injury was abrogated by ovariectomy with an associated increase in nitric oxide production. Males showed increased lung and gut injury after both T/HS and burns associated with increased production of nitrite/nitrate. Castration decreased susceptibility to both lung and gut injury, and decreased production of nitrite/nitrate. A correlation was noted between intestinal and lung injury, and both intestinal and lung injury correlated with plasma nitrite/nitrate levels.


CONCLUSIONS
Male sex hormones potentiate, while female hormones reduce T/HS and burn-induced lung and gut injury. Production of nitric oxide is associated with increased lung and gut injury after T/HS and burns.
Ananthakrishnan
Preya
P
Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Cohen
David B
DB
Xu
Da Zhong
DZ
Lu
Qi
Q
Feketeova
Eleonora
E
Deitch
Edwin A
EA
D000818:Animals; D002056:Burns / Q000378:metabolism / Q000503:physiopathology*; D004396:Coloring Agents / Q000493:pharmacokinetics; D004958:Estradiol / Q000502:physiology*; D005070:Evans Blue / Q000493:pharmacokinetics; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D009919:Orchiectomy; D010052:Ovariectomy; D011359:Proestrus; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000503:physiopathology*; D013047:Specific Pathogen-Free Organisms; D013739:Testosterone / Q000502:physiology*
D004396:Coloring Agents; D009569:Nitric Oxide; D013739:Testosterone; D005070:Evans Blue; D004958:Estradiol