Transition of Rat Pancreatic Juice Edema into Acute Pancreatitis by Single Ethanol Administration

Letko, G; Nosofsky, T; Lessel, W; Siech, Marco

doi:10.1016/s0344-0338(11)80779-x

Cited by 15 publications

(10 citation statements)

References 12 publications

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“…As calculated by Ammann et al (1), only 5% of all alcohol abusers will develop alcoholic pancreatitis. Interestingly enough, this can also be observed in setups with animals where acute pancreatitis cannot be induced by alcohol itself (8,15,25). Therefore, additional factors accompanying alcohol intake must be coresponsible for the induction of the disease.…”

mentioning

confidence: 87%

Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL)

Siech

Zhou

Zhou³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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MG. Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL). Am J Physiol Gastrointest Liver Physiol 297: G1163-G1171, 2009. First published September 24, 2009 doi:10.1152/ajpgi.90468.2008.-Mechanisms leading to acute pancreatitis after a fat-enriched meal combined with excess alcohol are incompletely understood. We have studied the effects of alcohol and fat (VLDL) on pancreatic acinar cell (PAC) function, oxidative stress, and repair mechanisms by pancreatic stellate cells (PSC) leading to fibrogenesis. To do so, PAC (rat) were isolated and cultured up to 24 h. Ethanol and/or VLDL were added to PAC. We measured PAC function (amylase, lipase), injury (lactic dehydrogenase), apoptosis (TUNEL, Apo2.7, annexin V binding), oxidative stress, and lipid peroxidation (conjugated dienes, malondialdehyde, chemoluminescence); we also measured PSC proliferation (bromodeoxyuridine incorporation), matrix synthesis (immunofluorescence of collagens and fibronectin, fibronectin immunoassay), and fatty acids in PAC supernatants (gas chromatography). Within 6 h, cultured PAC degraded and hydrolyzed VLDL completely. VLDL alone (50 g/ml) and in combination with alcohol (0.2, 0.5, and 1% vol/vol) induced PAC injury (LDL, amylase, and lipase release) within 2 h through generation of oxidative stress. Depending on the dose of VLDL and alcohol, apoptosis and/or necrosis were induced. Antioxidants (Trolox, Probucol) reduced the cytotoxic effect of alcohol and VLDL. Supernatants of alcohol/VLDL-treated PAC stimulated stellate cell proliferation and extracellular matrix synthesis. We concluded that, in the presence of lipoproteins, alcohol induces acinar cell injury. Our results provide a biochemical pathway for the clinical observation that a fat-enriched meal combined with excess alcohol consumption can induce acinar cell injury (acute pancreatitis) followed by repair mechanisms (proliferation and increased matrix synthesis in PSC).ethanol; free radicals; pancreas THE MECHANISM OF ALCOHOLIC PANCREATITIS is incompletely understood. Despite the fact that about 40% of acute pancreatitis and 70% of chronic pancreatitis in humans are induced by alcohol, most alcoholics will never be affected by any of these diseases. As calculated by Ammann et al. (1), only 5% of all alcohol abusers will develop alcoholic pancreatitis. Interestingly enough, this can also be observed in setups with animals where acute pancreatitis cannot be induced by alcohol itself (8,15,25). Therefore, additional factors accompanying alcohol intake must be coresponsible for the induction of the disease. Some of these cofactors such as stimulation of pancreatic secretion and/or obstruction of pancreatic outflow have been experimentally observed by us and others (8,12,25,26).Clinical experience has taught us that a large number of patients presenting an acute event of alcoholic pancreatitis have drunk lots of alcohol together with an opulent (fat enriched) meal the day before onset of the disease. In the present ...

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confidence: 87%

Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL)

Siech

Zhou

Zhou³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Only the combination of all three factors induced pancreatic damage with interlobular edema, cellular inflammatory infiltrates, perilobular fat necrosis and parenchymal necrosis. In another study with the same animal model, this group administered ethanol intragastrically, intraperitoneally and intravenously and reported that the mode of ethanol administration is not relevant for development of acute pancreatitis [15]. In another protocol, stimulation of pancreatic secretion with caerulein together with acute ethanol application led to necrotizing acute pancreatitis.…”

Section: Effects Of Acute Alcohol Administration In Combination With mentioning

confidence: 99%

Animal Models in Alcoholic Pancreatitis — What Can We Learn?

2002

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“…However, the combination of caerulein hyperstimulation with an additional noxious factor, e.g. ischemia and alcohol [36, 37, 38], as well as short-term ductal obstruction [39]and repeated ductal obstructions [40]can aggravate the severity of pancreatitis. Similarly, low doses of caerulein which did not cause pancreatitis at normocalcemia did cause acute pancreatitis when serum calcium levels were increased [41].…”

Section: Potential Of Therapeutic Application Of Cholecystokinin Recementioning

confidence: 99%

Role of Cholecystokinin in the Development and Progression of Acute Pancreatitis and the Potential of Therapeutic Application of Cholecystokinin Receptor Antagonists

Niederau

Grendell

1999

Digestion

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This presentation reviews the role of cholecystokinin (CCK) as a contributory factor for the development and progression of acute pancreatitis (AP) and the perspective of CCK receptor antagonists for treatment of AP. High, supraphysiological concentrations of CCK induce AP in various species including man. There is also evidence that physiological increases in plasma CCK deteriorates AP in several animal models. The latter findings support the hypothesis that CCK plays a contributory or permissive role for the development of AP. The majorities of experimental studies show that the prophylactic and therapeutic use of CCK antagonists ameliorates AP. The latter effects were clearly shown for models of biliary AP in which plasma CCK is increased due to a feedback mechanism. However, CCK antagonists also had beneficial effects in models in which plasma CCK is not increased. In animal strains which do not have a CCK-A-receptor due to a genetic abnormality AP induced by a certain noxious factor does not develop to the same severity when compared to animals with a normal CCK-A-receptor. Thus, CCK acts as a permissive or contributory factor for the development and progression of AP. There is also evidence that CCK antagonists have a potential therapeutic benefit. Clinical studies will evaluate their therapeutic potential for patients with AP.

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Transition of Rat Pancreatic Juice Edema into Acute Pancreatitis by Single Ethanol Administration

Cited by 15 publications

References 12 publications

Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL)

Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL)

Animal Models in Alcoholic Pancreatitis — What Can We Learn?

Role of Cholecystokinin in the Development and Progression of Acute Pancreatitis and the Potential of Therapeutic Application of Cholecystokinin Receptor Antagonists

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