title: Intestinal barrier disruption as a cause of mortality in combined radiation and burn injury.
abstract: Nuclear disaster associated with combined radiation injury (CRI) and trauma or burns results in higher mortality than component injuries. Early death is caused by sequelae of gastrointestinal (GI) leakiness such as bacterial translocation and shock. We developed a murine model to characterize GI injury after CRI and determine the extent of barrier disruption. Animals received radiation (5.5 Gy) alone or with 15% total body surface area (TBSA) scald burn and were euthanized at 24, 48, and 72 h. Mesenteric lymph node homogenate was plated on tryptic soy agar to assess for bacterial translocation. Tight junction protein, occludin, was characterized by Western blot and immunofluorescence. Intestinal histology was evaluated, and apoptosis was quantified using histone-associated DNA fragmentation enzyme-linked immunosorbent assay and Western blot for caspase-3 and caspase-8. At 72 h, a 100-fold increase in bacterial growth after CRI was observed. Occludin colocalization was reduced by radiation exposure, with largest differences in CRI at 24 and 48 h. Histopathology exhibited increased apoptosis in radiation alone and CRI animals at 24 and 48 h (P < 0.05). Further evidence of apoptotic activity in CRI was seen at 48 h, with 3-fold increases in enzyme-linked immunosorbent assay detection relative to all groups and caspase-8 activity relative to radiation alone and sham (P < 0.05). Prolonged epithelial apoptosis and disruption of tight junctions likely contribute to gut leakiness after CRI. Subsequent bacterial translocation to mesenteric lymph node potentially leads to sepsis and death and could serve as a target for mitigating agents to improve survival from CRI.
authors.affiliation: *Burn and Shock Trauma Research Institute, and †Departments of Surgery, ‡Pathology, and §Microbiology and Immunology, Loyola University Chicago Health Sciences Division, Maywood, Illinois.
authors.forename: Stewart R
authors.initials: SR
authors.lastname: Carter
authors.forename: Anita
authors.initials: A
authors.lastname: Zahs
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Palmer
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Luis
authors.initials: L
authors.lastname: Ramirez
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
mesh_terms: D000818:Animals; D017209:Apoptosis; D018988:Bacterial Translocation; D002056:Burns / Q000150:complications / Q000401:mortality* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D007422:Intestines / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000401:mortality* / Q000503:physiopathology
chemical_list: D053148:Caspase 3; D053181:Caspase 8
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