title: The effect of p38 mitogen-activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats.
abstract: Hemorrhagic shock is a frequent cause of liver failure and often leads to a fatal outcome. Several studies have revealed that p38 MAPK is a key mediator in hemorrhagic damage of the primary organs through the activation of proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. However, the precise role of these factors in liver damage following hemorrhagic shock is unclear. In this study, we used FR167653, a specific inhibitor of p38 MAPK phosphorylation, to examine the role of p38 MAPK in liver damage occurring up to 5 hours after a hemorrhagic episode in a rat model. Activation of p38 MAPK in the liver as well as an increase in hepatic mRNA expression and serum concentrations of TNF-α and IL-1β occurred during the early phase after hemorrhage. Increased serum levels of hepatic enzymes, as well as histological damage and activated neutrophil accumulation in the liver, were observed in the late phase following hemorrhagic shock. FR167653 inhibited the inflammation-related hepatic injury following hemorrhagic shock. Bacterial lipopolysaccharide (LPS) derived from the gut appeared to have little effects on the hepatic damage. These results demonstrate that p38 MAPK activation is induced by hepatic ischemia during hemorrhagic shock and plays an important role both in the hepatic expression of proinflammatory cytokines and in the development of inflammation-related liver damage.
authors.affiliation: Department of Forensic Medicine, University of Occupational and Environmental Health, Japan, Yahata-Nishi, Kitakyushu, Japan. h-sato@med.uoeh-u.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sato
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000473:pathology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D011169:Portal Vein / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000097:blood / Q000150:complications* / Q000201:enzymology* / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D048051:p38 Mitogen-Activated Protein Kinases