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1 Surgery, University of Alabama at Birmingham, Birmingham, Alabama, United States
2 Surgery, University of Alabama at Birmingham, Birmingham, Alabama, United States; Birmingham, Alabama, United States
3 Surgery, Nippon Medical School, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: irshad.chaudry{at}ccc.uab.edu.
Although studies indicate that hemorrhagic shock and resuscitation produces hepatic damage by mechanisms involving adhesion molecule in endothelial cells and hepatocytes, it is not known if there is any difference in the extent of hepatic damage following bone fracture, soft-tissue trauma and hemorrhage (Fx-TH) between young and middle-aged animals. To study this, young (6-8 weeks) and middle-aged (approximately 12 months) C3H/HeN male mice were subjected to right lower leg fracture, soft tissue trauma, (i.e., midline laparotomy) and hemorrhage (blood withdrawal to decrease the blood pressure to 35 ± 5 mmHg for 90 min) followed by resuscitation with 4x the shed blood volume in the form of Ringer's lactate. The mice were euthanized 24 h later and liver tissues were harvested. Total bilirubin levels in hepatocyte extract increased markedly following Fx-TH in both groups of mice; however, the increase in middle-aged mice was significantly higher compared to young mice. TNF-
and IL-6 levels in hepatocyte extract following Fx-TH increased significantly in middle-aged mice, but remained unchanged in young mice. IL-10 levels significantly decreased in middle-aged mice following Fx-TH, but remained unchanged in young mice. Kupffer cells from middle-aged mice produced significantly higher IL-6 and IL-10 compared to young mice. The protein levels and mRNA expression of ICAM-1 in hepatocytes were also significantly higher in middle-aged mice compared to young mice following Fx-TH. These results collectively suggest that the extent of hepatic damage following Fx-TH is dependent on the age of the subject.
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