Abstract | BACKGROUND: METHODS: Male Sprague-Dawley rats were divided into 4 groups ( sham, FR-only, control, and FR-treated groups). The animals in the control and FR-treated groups were subjected to 30 minutes of warm ischemia with congestion of the gut. The FR-only and FR-treated groups received FR167653 (FR), which is a novel p38 MAPK inhibitor. The serum levels of aspartate transaminase, alanine transaminase, lactate dehydrogenase, tumor necrosis factor-alpha ( TNF-alpha), and interleukin-1beta (IL-1beta) were measured (each, n = 6). Liver tissue blood flow was measured at pre- ischemia, end- ischemia, and 30, 60, 90, and 120 minutes after reperfusion (each, n = 4). The liver tissues in the control and FR-treated groups were excised for p38 MAPK and c-Jun N-terminal kinase (JNK) analyses and histopathology (each, n = 4). RESULTS: Serum levels of aspartate transaminase, alanine transaminase, lactate dehydrogenase, TNF-alpha, and IL-1beta were significantly lower in the FR-treated group than in the control group, and liver tissue blood flow was significantly higher in the FR-treated group than in the control group. Histopathologically, tissue damage was milder in the FR-treated group than in the control group. Both p38 MAPK and JNK were markedly phosphorylated after 30 minutes of reperfusion, and FR inhibited the phosphorylation of p38 MAPK without affecting the JNK. CONCLUSIONS:
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Authors | Mitsunobu Kobayashi, Izumi Takeyoshi, Daisuke Yoshinari, Koshi Matsumoto, Yasuo Morishita |
Journal | Surgery
(Surgery)
Vol. 131
Issue 3
Pg. 344-9
(Mar 2002)
ISSN: 0039-6060 [Print] United States |
PMID | 11894041
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- FR 167653
- Interleukin-1
- Pyrazoles
- Pyridines
- Tumor Necrosis Factor-alpha
- Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Enzyme Inhibitors
(pharmacology)
- Interleukin-1
(blood)
- Ischemia
(pathology, physiopathology)
- Liver
(drug effects, pathology)
- Liver Circulation
(drug effects)
- Male
- Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism, physiology)
- Phosphorylation
(drug effects)
- Pyrazoles
(pharmacology)
- Pyridines
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(pathology, physiopathology)
- Tumor Necrosis Factor-alpha
(analysis)
- p38 Mitogen-Activated Protein Kinases
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