The effect of p38 mitogen-activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats.
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 interleuk...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3253806?pdf=render |
| _version_ | 1819069248142573568 |
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| author | Hiroaki Sato Toshiko Tanaka Noriyuki Tanaka |
| author_facet | Hiroaki Sato Toshiko Tanaka Noriyuki Tanaka |
| author_sort | Hiroaki Sato |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T16:47:01Z |
| format | Article |
| id | doaj.art-7d4afe1237954aada55d72838eac7327 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T16:47:01Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-7d4afe1237954aada55d72838eac73272022-12-21T18:56:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0171e3012410.1371/journal.pone.0030124The effect of p38 mitogen-activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats.Hiroaki SatoToshiko TanakaNoriyuki TanakaHemorrhagic 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.http://europepmc.org/articles/PMC3253806?pdf=render |
| spellingShingle | Hiroaki Sato Toshiko Tanaka Noriyuki Tanaka The effect of p38 mitogen-activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats. PLoS ONE |
| title | The effect of p38 mitogen-activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats. |
| title_full | The effect of p38 mitogen-activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats. |
| title_fullStr | The effect of p38 mitogen-activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats. |
| title_full_unstemmed | The effect of p38 mitogen-activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats. |
| title_short | The effect of p38 mitogen-activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats. |
| title_sort | effect of p38 mitogen activated protein kinase activation on inflammatory liver damage following hemorrhagic shock in rats |
| url | http://europepmc.org/articles/PMC3253806?pdf=render |
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