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Oxidative stress in acute pancreatitis.
Hepatogastroenterology. 1999 Sep-Oct; 46(29):2736-50.H

Abstract

The present work critically reviews the evidence for an involvement of free radicals in the pathophysiology of acute pancreatitis and the potential of treatment with antioxidants and scavenger substances. Data originating from clinical trials, experimental pancreatitis studies and in vitro investigations are included. Enhanced free radical activities and increased concentrations of lipid peroxides in plasma and tissue have been found in both patients and experimental animals with acute pancreatitis. The individual contribution of possible sources of free radicals (e.g., invading inflammatory cells, xanthine oxidase, cytochromes P450, nitric oxide synthase) is not yet clear, however. Since prophylactic administration of antioxidants diminished, in particular, pancreatic edema formation, free radicals seem to play an important role in the genesis of edema in acute pancreatitis. An involvement of free radicals in the pathogenesis of pancreatic necrosis could not yet be proven. Thus, no antioxidant treatment has proven useful for therapy of fulminant pancreatitis in animals to date. However, in severe acute pancreatitis characterized by death occurring after 12-18 hours, the seleno-organic compound Ebselen, which has a glutathione peroxidase-like activity, and the membrane permeable ascorbic acid derivative CV-3611 have been demonstrated to be effective. To date, controlled clinical studies have failed to demonstrate the therapeutic efficacy of antioxidant selenium or glutathione precursor supplementation. Therefore, further controlled clinical trials are needed to determine whether supplements of antioxidants can alter the clinical course of acute pancreatitis. Since the nitric oxide radical may even protect the pancreas, a purely negative discussion of the role of free radicals on the pancreas is not justified. The actual role of free radicals in acute pancreatitis, i.e. serving the body's defense against infection, being an epiphenomenon of the inflammatory process without pathophysiological relevance, or having true pathogenic significance, is not yet clear. Lipid peroxidation may perhaps not be the cause but rather the sequel of pancreatic inflammation and may likely reflect the severity of the systemic inflammatory response rather than that of pancreatic parenchyma damage. In vitro, exposure of isolated pancreatic acinar cells to oxidative stress caused rapid cell damage and death. Such knowledge from cellular studies might help to plan therapeutical trials to evaluate potentially effective therapies in the experimental animal, as well as in patients suffering from pancreatitis. Thus, to further clarify the role of oxidative stress in acute pancreatitis, an integrated approach is needed, including investigations at various biological levels, from isolated cells or even organelles to laboratory animals and, finally, clinical studies in man.

Authors+Show Affiliations

Department of Surgery, Otto-von-Guericke-University of Magdeburg, Germany. hans-ulrich.schulz@medizin.uni-magdeburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

10576339

Citation

Schulz, H U., et al. "Oxidative Stress in Acute Pancreatitis." Hepato-gastroenterology, vol. 46, no. 29, 1999, pp. 2736-50.
Schulz HU, Niederau C, Klonowski-Stumpe H, et al. Oxidative stress in acute pancreatitis. Hepatogastroenterology. 1999;46(29):2736-50.
Schulz, H. U., Niederau, C., Klonowski-Stumpe, H., Halangk, W., Luthen, R., & Lippert, H. (1999). Oxidative stress in acute pancreatitis. Hepato-gastroenterology, 46(29), 2736-50.
Schulz HU, et al. Oxidative Stress in Acute Pancreatitis. Hepatogastroenterology. 1999 Sep-Oct;46(29):2736-50. PubMed PMID: 10576339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative stress in acute pancreatitis. AU - Schulz,H U, AU - Niederau,C, AU - Klonowski-Stumpe,H, AU - Halangk,W, AU - Luthen,R, AU - Lippert,H, PY - 1999/11/27/pubmed PY - 1999/11/27/medline PY - 1999/11/27/entrez SP - 2736 EP - 50 JF - Hepato-gastroenterology JO - Hepatogastroenterology VL - 46 IS - 29 N2 - The present work critically reviews the evidence for an involvement of free radicals in the pathophysiology of acute pancreatitis and the potential of treatment with antioxidants and scavenger substances. Data originating from clinical trials, experimental pancreatitis studies and in vitro investigations are included. Enhanced free radical activities and increased concentrations of lipid peroxides in plasma and tissue have been found in both patients and experimental animals with acute pancreatitis. The individual contribution of possible sources of free radicals (e.g., invading inflammatory cells, xanthine oxidase, cytochromes P450, nitric oxide synthase) is not yet clear, however. Since prophylactic administration of antioxidants diminished, in particular, pancreatic edema formation, free radicals seem to play an important role in the genesis of edema in acute pancreatitis. An involvement of free radicals in the pathogenesis of pancreatic necrosis could not yet be proven. Thus, no antioxidant treatment has proven useful for therapy of fulminant pancreatitis in animals to date. However, in severe acute pancreatitis characterized by death occurring after 12-18 hours, the seleno-organic compound Ebselen, which has a glutathione peroxidase-like activity, and the membrane permeable ascorbic acid derivative CV-3611 have been demonstrated to be effective. To date, controlled clinical studies have failed to demonstrate the therapeutic efficacy of antioxidant selenium or glutathione precursor supplementation. Therefore, further controlled clinical trials are needed to determine whether supplements of antioxidants can alter the clinical course of acute pancreatitis. Since the nitric oxide radical may even protect the pancreas, a purely negative discussion of the role of free radicals on the pancreas is not justified. The actual role of free radicals in acute pancreatitis, i.e. serving the body's defense against infection, being an epiphenomenon of the inflammatory process without pathophysiological relevance, or having true pathogenic significance, is not yet clear. Lipid peroxidation may perhaps not be the cause but rather the sequel of pancreatic inflammation and may likely reflect the severity of the systemic inflammatory response rather than that of pancreatic parenchyma damage. In vitro, exposure of isolated pancreatic acinar cells to oxidative stress caused rapid cell damage and death. Such knowledge from cellular studies might help to plan therapeutical trials to evaluate potentially effective therapies in the experimental animal, as well as in patients suffering from pancreatitis. Thus, to further clarify the role of oxidative stress in acute pancreatitis, an integrated approach is needed, including investigations at various biological levels, from isolated cells or even organelles to laboratory animals and, finally, clinical studies in man. SN - 0172-6390 UR - https://www.unboundmedicine.com/medline/citation/10576339/Oxidative_stress_in_acute_pancreatitis_ L2 - http://www.diseaseinfosearch.org/result/9663 DB - PRIME DP - Unbound Medicine ER -