Alcoholic pancreatitis in rats: injury from nonoxidative metabolites of ethanol

2002 ◽  
Vol 283 (1) ◽  
pp. G65-G73 ◽  
Author(s):  
Jens Werner ◽  
Mouris Saghir ◽  
Andrew L. Warshaw ◽  
Kent B. Lewandrowski ◽  
Michael Laposata ◽  
...  
Keyword(s):  
Cell Damage ◽  
Acid Ethyl Ester ◽  
Fatty Acid Ethyl Ester ◽  
Pancreatic Injury ◽  
Ethanol Metabolism ◽  
Alcoholic Pancreatitis ◽  
Pancreatic Cell ◽  
Pancreatic Acini ◽  
Trypsinogen Activation

The mechanism by which alcohol injures the pancreas remains unknown. Recent investigations suggest a role for fatty acid ethyl ester (FAEE), a nonoxidative metabolite of ethanol, in the pathogenesis of alcohol pancreatitis. In this study, we characterized ethanol-induced injury in rats and evaluated the contribution of oxidative and nonoxidative ethanol metabolites in this form of acute pancreatitis. Pancreatic injury in rats was assessed by edema, intrapancreatic trypsinogen activation, and microscopy after infusing ethanol with or without inhibitors of oxidative ethanol metabolism. Plasma and tissue levels of FAEE and ethanol were measured and correlated with pancreatic injury. Ethanol infusion generated plasma and tissue FAEE and, in a dose-dependent fashion, induced a pancreas-specific injury consisting of edema, trypsinogen activation, and formation of vacuoles in the pancreatic acini. Inhibition of the oxidation of ethanol significantly increased both FAEE concentration in plasma and pancreas and worsened the pancreatitis-like injury. This study provides direct evidence that ethanol, through its nonoxidative metabolic pathway, can produce pancreas-specific toxicity in vivo and suggests that FAEE are responsible for the development of early pancreatic cell damage in acute alcohol-induced pancreatitis.

scholarly journals Fatty acid ethyl ester synthase, an enzyme for nonoxidative ethanol metabolism, is present in serum after liver and pancreatic injury

1996 ◽  
Vol 42 (1) ◽  
pp. 24-27 ◽  
Author(s):  
S Aleryani ◽  
A Kabakibi ◽  
J Cluette-Brown ◽  
M Laposata
Keyword(s):  
Fatty Acid ◽  
Aspartate Aminotransferase ◽  
Acid Ethyl Ester ◽  
Fatty Acid Ethyl Ester ◽  
Pancreatic Injury ◽  
Pancreatic Disease ◽  
Ethyl Esters ◽  
Ethanol Metabolism ◽  
Gas Chromatography Mass Spectrometry ◽  
Pancreatic Damage

Abstract Fatty acid ethyl esters (FAEE), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol-induced organ damage. Because cytosolic enzymes such as aspartate aminotransferase, lipase, and amylase appear in the blood after liver or pancreatic damage, we hypothesized that FAEE synthase, which is both cytosolic and membrane bound, is also released into the blood of patients with liver or pancreatic disease. We used a method involving thin-layer chromatography coupled with gas chromatography-mass spectrometry to reliably identify and quantify FAEE. In this study, we demonstrated that patients with liver or pancreatic disease release FAEE synthase into their plasma in amounts proportional to the amount of aspartate aminotransferase (r = 0.78), amylase (r = 0.65), and lipase (r = 0.63). These data indicate that liver and pancreatic damage results in release of FAEE synthase into the blood. The presence of FAEE synthase in plasma permits nonoxidative ethanol metabolism in the plasma.

PATHOPHYSIOLOGY AND BIOMARKER POTENTIAL OF FATTY ACID ETHYL ESTER ELEVATION DURING ALCOHOLIC PANCREATITIS

2021 ◽  
Author(s):  
Stacie Vela ◽  
Andre Guerra ◽  
Gail Farrell ◽  
Shubham Trivedi ◽  
Hally Chaffin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Ethyl Ester ◽  
Acid Ethyl Ester ◽  
Fatty Acid Ethyl Ester ◽  
Alcoholic Pancreatitis

Nonoxidative ethanol metabolism: Expression of fatty acid ethyl ester synthase-III in cultured neural cells

1992 ◽  
Vol 185 (3) ◽  
pp. 938-943 ◽  
Author(s):  
Keith E. Isenberg ◽  
Puran S. Bora ◽  
Xia Zhou ◽  
Xiaolin Wu ◽  
Blake W. Moore ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Ethyl Ester ◽  
Acid Ethyl Ester ◽  
Fatty Acid Ethyl Ester ◽  
Ethanol Metabolism ◽  
Neural Cells

Pancreatic injury in rats induced by fatty acid ethyl ester, a nonoxidative metabolite of alcohol

1997 ◽  
Vol 113 (1) ◽  
pp. 286-294 ◽  
Author(s):  
J Werner ◽  
M Laposata ◽  
C Fernandez-del Castillo ◽  
M Saghir ◽  
RV Iozzo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Ethyl Ester ◽  
Acid Ethyl Ester ◽  
Fatty Acid Ethyl Ester ◽  
Pancreatic Injury

Dopamine D2 receptor activator quinpirole protects against trypsinogen activation during acute pancreatitis via upregulating HSP70

2020 ◽  
Vol 318 (6) ◽  
pp. G1000-G1012
Author(s):  
Xin Ye ◽  
Xiao Han ◽  
Bin Li ◽  
Juanjuan Dai ◽  
Zengkai Wu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Pancreatic Injury ◽  
Dependent Manner ◽  
Trypsinogen Activation ◽  
Mechanistic Insight ◽  
Receptor Activator

The current study demonstrated that activation of DRD2 by quinpirole protects against trypsinogen activation in the in vitro and in vivo setting of acute pancreatitis by upregulating HSP70 and restoring lysosomal degradation via a PP2A-dependent manner, therefore leading to reduced pancreatic injury. These findings provide a new mechanistic insight on the protective effect of DRD2 activation in acute pancreatitis.

Ethanol differentially regulates NF-κB activation in pancreatic acinar cells through calcium and protein kinase C pathways

2004 ◽  
Vol 286 (2) ◽  
pp. G204-G213 ◽  
Author(s):  
Anna S. Gukovskaya ◽  
Saeed Hosseini ◽  
Akihiko Satoh ◽  
Jason H. Cheng ◽  
Kyung J. Nam ◽  
...  
Keyword(s):  
Acinar Cells ◽  
Inhibitory Effect ◽  
Pancreatic Acinar Cells ◽  
Alcoholic Pancreatitis ◽  
Pancreatic Acini ◽  
Intracellular Ca ◽  
Ethanol Feeding ◽  
Ethanol Ethanol

Mechanisms of alcoholic pancreatitis remain unknown. Previously, we showed that ethanol feeding sensitizes rats to pancreatitis caused by CCK-8, at least in part, by augmenting activation of the proinflammatory transcription factor NF-κB. To elucidate the mechanism of sensitization, here we investigate the effect of ethanol on Ca2+- and PKC-mediated pathways of CCK-induced NF-κB activation using an in vitro system of rat pancreatic acini incubated with ethanol. Ethanol augmented CCK-8-induced activation of NF-κB, similar to our in vivo findings with ethanol-fed rats. In contrast, ethanol prevented NF-κB activation caused by thapsigargin, an agent that mobilizes intracellular Ca2+ bypassing the receptor. Pharmacological analysis showed that NF-κB activation by thapsigargin but not by CCK-8 is mediated through the calcineurin pathway and that the inhibitory effect of ethanol on the thapsigargin-induced NF-κB activation could be through inhibiting this pathway. Ethanol augmented NF-κB activation induced by the phorbol ester PMA, a direct activator of PKC. Inhibitory analysis demonstrated that Ca2+-independent (novel and/or atypical) PKC isoforms are involved in NF-κB activation induced by both CCK-8 and PMA in cells treated and not treated with ethanol. The results indicate that ethanol differentially affects the Ca2+/calcineurin- and PKC-mediated pathways of NF-κB activation in pancreatic acinar cells. These effects may play a role in the ability of ethanol to sensitize pancreas to the inflammatory response and pancreatitis.

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