Burns : journal of the International Society for Burn Injuries
-
This study was made to evaluate the effect of SB203580, a specific p38 MAP kinase inhibitor, on burn-induced hepatic injury as well as the activation of nuclear factor (NF)-kappaB in severely burned rats. Sprague-Dawley rats were divided into three groups: (1) sham group, rats underwent sham burn; (2) burn group, rats given third-degree burns over 30% total body surface area (TBSA) and treated with vehicle plus lactated Ringer solution for resuscitation 4 ml/(kg% TBSA); and (3) burn plus SB203580 group, rats given burn injury and fluid resuscitation plus SB203580 (10 mg/kg i.v., 15 min and 12 h after burn). Hepatocellular injury (measured by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and hepatocellular function (determined by the indocyanine green dye retention rate (ICG R15)) were assessed at 24 h post-burn. ⋯ SB203580 inhibited the activation of p38 MAP kinase, reduced the levels of TNF-alpha and IL-1beta, and prevented burn-mediated liver injury. Both the IkappaBalpha level and NF-kappaB activity in the liver following burns was not affected by administration with SB203580. These findings suggest that (1) p38 MAP kinase activation is one important aspect of the signaling event that may mediate the release of TNF-alpha and IL-1beta and contributes to burn-induced liver injury and (2) p38 MAP kinase does not influence the activation of NF-kappaB directly in the liver of severely burned rats.
-
Previous studies from our laboratory have shown that acute alcohol (EtOH) ingestion prior to burn injury enhances intestinal bacterial translocation. This study tested if increased intestinal bacterial translocation in alcohol and burn injured rats is due to an overgrowth in intestinal bacteria. We determined if the translocation was accompanied with alterations in intestinal permeability and immune cell population. ⋯ The increase in intestinal bacterial counts accompanied a significant increase in intestinal permeability. Finally, immunohistochemical analysis revealed a substantial (p<0.05) loss of both T cell and dendritic cells in intestine of alcohol and burn injured rats compared with intestine of rats receiving either burn or sham injury. Altogether, results presented in this manuscript suggest that increase in intestinal bacterial growth along with alterations in intestinal permeability and immune status contribute to the increase in bacterial translocation observed in alcohol and burn injured rats.