Fatty acid ethyl ester (FAEE) associated acute pancreatitis: An ex-vivo study using human pancreatic acini
| Autor: | Rupjyoti Talukdar, R. Pradeep, G Venkat Rao, Ramaiah Jangala, Balkumar Reddy, R. B. Reddy, D. Nageshwar Reddy, Aparna Jakkampudi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism medicine.medical_treatment Apoptosis Acinar Cells Cathepsin B Internal medicine Zymogen Acinar cell medicine Humans Pancreas Hepatology business.industry Fatty Acids Gastroenterology Esters Trypsin Cytokine Endocrinology Pancreatitis Tumor necrosis factor alpha business Ex vivo medicine.drug |
| Zdroj: | Pancreatology. 20:1620-1630 |
| ISSN: | 1424-3903 |
| Popis: | Background & aim Fatty acid ethyl esters (FAEEs), are produced by non-oxidative alcohol metabolism and can cause acinar cell damage and subsequent acute pancreatitis in rodent models. Even though experimental studies have elucidated the FAEE mediated early intra-acinar events, these mechanisms have not been well studied in humans. In the present study, we evaluate the early intra-acinar events and inflammatory response in human pancreatic acinar tissues and cells in an ex-vivo model. Methods Experiments were conducted using normal human pancreatic tissues exposed to FAEE. Subcellular fractionation was performed on tissue homogenates and trypsin and cathepsin B activities were estimated in these fractions. Acinar cell injury was evaluated by histology and immunohistochemistry. Cytokine release from exposed acinar cells was evaluated by performing Immuno-fluorescence. Serum was collected from patients with AP within the first 72 h of symptom onset for cytokine estimation using FACS. Results We observed significant trypsin activation and acinar cell injury in FAEE treated tissue. Cathepsin B was redistributed from lysosomal to zymogen compartment at 30 min of FAEE exposure. IHC results indicated the presence of apoptosis in pancreatic tissue at 1 & 2hrs of FAEE exposure. We also observed a time dependent increase in secretion of cytokines IL-6, IL-8, TNF-α from FAEE treated acinar tissue. There was also a significant elevation in plasma cytokines in patents with alcohol associated AP within 72 h of symptom onset. Conclusion Our data suggest that alcohol metabolites can cause acute acinar cell damage and subsequent cytokine release which could eventually culminant in SIRS. |
| Databáze: | OpenAIRE |
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