title: Testosterone depletion or blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph.
abstract: BACKGROUND
  We tested the hypothesis that testosterone depletion or blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph.
  
  
  METHODS
  Male, castrated male, or flutamide-treated rats (25 mg/kg subcutaneously after resuscitation) were subjected to a laparotomy (trauma), mesenteric lymph duct cannulation, and 90 minutes of shock (35 mm Hg) or trauma sham-shock. Mesenteric lymph was collected preshock, during shock, and postshock. Gut injury was determined at 6 hours postshock using ex vivo ileal permeability with fluorescein dextran. Postshock mesenteric lymph was assayed for biological activity in vivo by injection into mice and measuring lung permeability, neutrophil activation, and red blood cell deformability. In vitro neutrophil priming capacity of the lymph was also tested.
  
  
  RESULTS
  Castrated and flutamide-treated male rats were significantly protected against trauma hemorrhagic shock (T/HS)-induced gut injury when compared with hormonally intact males. Postshock mesenteric lymph from male rats had a higher capacity to induce lung injury, Neutrophil (PMN) activation, and loss of red blood cell deformability when injected into naïve mice when compared with castrated and flutamide-treated males. The increase in gut injury after T/HS in males directly correlated with the in vitro biological activity of mesenteric lymph to prime neutrophils for an increased respiratory burst.
  
  
  CONCLUSIONS
  After T/HS, gut protective effects can be observed in males after testosterone blockade or depletion. This reduced gut injury contributes to decreased biological activity of mesenteric lymph leading to attenuated systemic inflammation and distant organ injury.
authors.affiliation: Department of Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
authors.forename: Sharvil U
authors.initials: SU
authors.lastname: Sheth
authors.forename: David
authors.initials: D
authors.lastname: Palange
authors.forename: Da-Zhong
authors.initials: DZ
authors.lastname: Xu
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.forename: Eleonora
authors.initials: E
authors.lastname: Feketeova
authors.forename: Qi
authors.initials: Q
authors.lastname: Lu
authors.forename: Diego C
authors.initials: DC
authors.lastname: Reino
authors.forename: Xiaofa
authors.initials: X
authors.lastname: Qin
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
mesh_terms: D000818:Animals; D002369:Castration / Q000379:methods; D004195:Disease Models, Animal; D005485:Flutamide / Q000494:pharmacology; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000503:physiopathology*; D055370:Lung Injury / Q000378:metabolism / Q000503:physiopathology*; D008196:Lymph / Q000187:drug effects / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000378:metabolism; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012720:Severity of Illness Index; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000502:physiology; D015996:Survival Rate; D013739:Testosterone / Q000172:deficiency* / Q000378:metabolism
chemical_list: D013739:Testosterone; D005485:Flutamide