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Liver injury during acute pancreatitis: the role of pancreatitis-associated ascitic fluid (PAAF), p38-MAPK, and caspase-3 in inducing hepatocyte apoptosis.
- Source :
-
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract [J Gastrointest Surg] 2003 Feb; Vol. 7 (2), pp. 200-7; discussion 208. - Publication Year :
- 2003
-
Abstract
- We have demonstrated that pancreatitis-associated ascitic fluid contributes to hepatocyte injury during acute pancreatitis; a phenomenon independent of ascites' enzymatic content and Kupffer cell-derived cytokines. Our aim is to characterize the mechanisms of pancreatitis-associated ascitic fluid induced hepatocyte death. NIH mice were injected intraperitoneally with pathogen-free pancreatitis-associated ascitic fluid. Twenty-four hours later, serum AST, ALT, LDH, and hepatocyte apoptosis (TUNEL) were measured. Human hepatocytes (CCL-13) were treated with pancreatitis-associated ascitic fluid +/-SB203580 or caspase-3 inhibitor-II. Mitochondrial membrane integrity was determined by DiOC6 staining. Apoptosis was measured by TUNEL staining and flow cytometry after dual labeling with Annexin-V/7-AAD. Data are mean +/- SEM of triplicates. Pancreatitis-associated ascitic fluid increased serum AST, ALT, LDH, and apoptotic cells in the mouse liver (all P < 0.03 vs. sham). In CCL-13 cells, pancreatitis-associated ascitic fluid induced a time and dose-dependent increase in apoptosis, in addition to p38-MAPK phosphorylation (P = 0.02 vs. control), caspase-3 cleavage (P < 0.03 vs. control) and decreased DiOC6 mitochondrial staining (P < 0.01 vs. control). Both caspase-3 inhibitor-II and SB203580 decreased apoptosis, but the former had no effect on DiOC6 staining. Pancreatitis-associated ascitic fluid induces liver injury and hepatocyte apoptosis by activating p38-MAPK and caspase-3 dependent pro-apoptotic pathways.
- Subjects :
- Acute Disease
Animals
Ascitic Fluid cytology
Biomarkers analysis
Caspase 3
Cells, Cultured
Disease Models, Animal
Liver Diseases etiology
Male
Probability
Random Allocation
Rats
Rats, Sprague-Dawley
Reference Values
Sensitivity and Specificity
p38 Mitogen-Activated Protein Kinases
Apoptosis
Ascitic Fluid physiopathology
Caspases metabolism
Hepatocytes metabolism
Liver enzymology
Liver pathology
Liver Diseases pathology
Mitogen-Activated Protein Kinases metabolism
Pancreatitis complications
Subjects
Details
- Language :
- English
- ISSN :
- 1091-255X
- Volume :
- 7
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
- Publication Type :
- Academic Journal
- Accession number :
- 12600444
- Full Text :
- https://doi.org/10.1016/s1091-255x(02)00134-8