Abstract
Background. Several studies have implicated the mitogen-activated protein kinase (MAPK) signal
pathway in non-hepatic organ ischemia-reperfusion injury. However, the role of p38
MAPK in hepatic ischemia-reperfusion injury remains unclear. This study investigated
the role of p38 MAPK in hepatic ischemia-reperfusion injury. 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-α (TNF-α), and interleukin-1β (IL-1β) 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-α, and IL-1β 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. FR decreased serum TNF-α and IL-1β levels and liver injury associated with the inhibition
of p38 MAPK activation. These results suggest that inhibiting the activation of p38
MAPK may attenuate warm ischemia-reperfusion injury of the liver. (Surgery 2002;131:344-9.)
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Article info
Publication history
Accepted:
September 22,
2001
Footnotes
*This work was supported in part by a fund from Fujisawa Pharmaceutical Co Ltd, Osaka, Japan.
**Reprint requests: Izumi Takeyoshi, Second Department of Surgery, Gunma University School of Medicine, 3-39-15, Showa Machi, Maebashi, Gunma 371-8511, Japan.
Identification
Copyright
© 2002 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
