Testosterone depletion / 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
| Autor: | Da-Zhong Xu, Edwin A. Deitch, Eleonora Feketeova, Qi Lu, Xiaofa Qin, Dong Wei, David Palange, Diego Reino, Sharvil U. Sheth |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Resuscitation Lung injury Shock Hemorrhagic Critical Care and Intensive Care Medicine Severity of Illness Index Article Neutrophil Activation Rats Sprague-Dawley Random Allocation In vivo Reference Values Internal medicine medicine Animals Testosterone Castration Splanchnic Circulation Lymphatic Vessels Lung business.industry Lung Injury Flutamide Respiratory burst Rats Gastrointestinal Tract Survival Rate Disease Models Animal Endocrinology medicine.anatomical_structure Shock (circulatory) Surgery Lymph medicine.symptom business Ex vivo |
| Popis: | 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 naive 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. |
| Databáze: | OpenAIRE |
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