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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies in animal models suggest that oxygen radicals may be important in the pathogenesis of acute pancreatitis. Because glutathione is an essential component of the defense against radical-mediated cellular injury, we investigated whether pancreatic glutathione content is influenced by inducing acute pancreatitis and whether augmenting the intracellular supply of glutathione would alter the course of pancreatitis. Caerulein, a decapeptide cholecystokinin analogue, induces acute necrotizing pancreatitis in mice when given in high doses (50 micrograms/kg per h) over a period of 6 h. The pancreatic glutathione content (total, GSH + GSSG) in mice treated with high-dose caerulein fell to 17% of normal within 4 h of beginning caerulein and recovered toward normal after discontinuing caerulein treatment. Mice treated with glutathione monoethyl ester (20 mmol/kg 1 h before caerulein, 10 mmol/kg 3 and 7 h after starting caerulein) were found to have blunted depletion of pancreatic glutathione, diminished histologic evidence of pancreatitis (necrosis, inflammation, and vacuolization), and lower serum amylase values compared with mice treated with caerulein alone. These findings suggest that the profound depletion of pancreatic glutathione caused by hyperstimulation of the pancreas with caerulein is critically important in the pathogenesis of acute caerulein-induced pancreatitis.
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PMID:Glutathione monoethyl ester ameliorates caerulein-induced pancreatitis in the mouse. 137 Feb 92

In this prospective study the free radical mediated reactions, the changes of endogenous antioxidant defense mechanism and activation of leukocytes were measured from the blood of patients undergoing elective cholecystectomy because of symptomatic cholecystolithiasis. The patients were randomised into two groups. Group one contained 21 patients treated by open cholecystectomy(OC). Group two consisted of 21 patients treated by laparoscopic cholecystectomy (LC). Both groups had similar patient characteristics. Patients with acute cholecystitis, pancreatitis, choledocholithiasis or other disease were excluded. Values from patients in both groups were compared. The measured biochemical parameters are the following: malondialdehyde (MDA) as a marker of the free radical induced lipid peroxidations, reduced and oxidised glutathione (GSH-GSSG), as endogenous scavengers as well as markers of oxidative stress and myeloperoxidase activity (MPO) of leukocytes. The results showed significantly lower values of postoperatively measured MDA, GSH-GSSG, and MPO activity of leukocytes in patients with laparoscopic cholecystectomy, indicating a lesser stress response and tissue trauma in this group of patients. The results correspond to the favourable results of most other trials evaluating clinical aspect of LC.
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PMID:Inflammatory mediators and surgical trauma regarding laparoscopic access: free radical mediated reactions. 940 2

Oxidative stress has been proposed to play a role in the early events of acute pancreatitis, and metallothionein (MT) can provide protection against oxidative stress. Using transgenic mice, we characterized the effects of depletion of MT-I and -II, or overexpression of MT-I, on pancreatic responses during cerulein-induced acute pancreatitis. In MT-I/-II knockout mice, repeated injections of cerulein caused (a) higher serum amylase levels at 3 and 7 h after the initiation of acute pancreatitis; (b) earlier and stronger upregulation of oxidative stress-responsive genes, including heme oxygenase (HO)-1 and c-fos; and (c) exacerbated tissue damage (edema and polymorphonuclear neutrophil infiltration) compared with nontransgenic 129/SvCPJ mice. Total pancreatic glutathione (GSH + GSSG) content was similar between the knockout and nontransgenic 129/SvCPJ mice. Interestingly, during acute pancreatitis, CD-1 mice pretreated with L-buthionine-[S,R]-sulfoximine (BSO), which dramatically depleted pancreatic GSH, also had more severe pancreatitis, based on the same three criteria listed above, relative to untreated controls. No effects were observed with BSO treatment alone. Finally, during cerulein-induced acute pancreatitis, MT-I overexpressing transgenic mice (>20-fold increase in pancreatic MT-I content) had lower serum alpha-amylase levels between 7 and 24 h and delayed upregulation of HO-1 mRNA levels, but no difference in c-fos mRNA induction relative to the appropriate strain of nontransgenic mice. Diminished tissue damage (particularly cellular necrosis) was noted in these MT-I overexpressing transgenic mice. Total pancreatic GSH content was similar in these transgenic and nontransgenic mice during cerulein-induced acute pancreatitis. These studies suggest that pancreatic MT can function as an intracellular antioxidant as does GSH and that these intracellular antioxidants play a protective role during cerulein-induced acute pancreatitis.
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PMID:Metallothionein protects against cerulein-induced acute pancreatitis: analysis using transgenic mice. 978 36

Various protocols may be used for acute pancreatitis treatment. Recently, the benefit of hyperbaric oxygen (HBO) has been demonstrated. To clarify the mechanism of HBO on the process of the acute pancreatitis, we determined the levels of antioxidant enzymes in an acute pancreatitis model. Forty-five Sprague-Dawley rats were randomly divided into three groups: Group I: sham group (n=15), Group II: pancreatitis group (n=15), Group III: pancreatitis group undergoing HBO therapy (n=15). HBO was applied postoperatively for 5 days, two sessions per day at 2.5 fold absolute atmospheric pressure (ATA) for 90 min. Superoxide dismutase (Cu/Zn-SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH Px) activity were measured in pancreatic tissue and erythrocyte lysate. MDA and GSH Px were also determined in plasma. In addition, amylase levels were measured in the serum. While serum amylase levels and MDA values in erythrocyte, plasma and pancreatic tissue were decreased, the levels of GSH Px and SOD were found to be significantly increased in the Group III as compared to those of the Group II. The findings of our study suggest that HBO has beneficial effects on the course of acute pancreatitis and this effect may occur through the antioxidant systems.
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PMID:The effect of hyperbaric oxygen treatment on oxidative stress in experimental acute necrotizing pancreatitis. 1262 15

Increased lipid peroxidation, enhanced nuclear factor kappa-B (NF-kappaB) activation and augmented tumor necrosis factor-alpha (TNF-alpha) production have been implicated in cerulein-induced pancreatitis. We investigated whether lipid peroxidation inhibition might reduce NF-kappaB activation and the inflammatory response in cerulein-induced pancreatitis. Male Sprague-Dawley rats of 230-250g body weight received administration of cerulein (80 microg/kg s.c. for each of four injections at hourly intervals). A control group received four s.c. injections of 0.9% saline at hourly intervals. Animals were randomized to receive either raxofelast, an inhibitor of lipid peroxidation (20 mg/kg i.p. administered with the first cerulein injection) or its vehicle (1 ml/kg of a 10% DMSO/NaCl solution). All these rats were sacrificed 2 h after the last injection of either cerulein or its vehicle. Raxofelast administration (20 mg/kg i.p. with the first cerulein) significantly reduced malondialdehyde (MDA) levels, an index of lipid peroxidation (CER + DMSO = 3.075 +/- 0.54 micromol/g; CER + raxofelast = 0.693 +/- 0.18 micromol/g; p < 0.001), decreased myeloperoxidase (MPO) activity (CER + DMSO = 22.2 +/- 3.54 mU/g; CER + raxofelast = 9.07 +/- 2.05 mU/g, p < 0.01), increased glutathione levels (GSH) (CER + DMSO = 5.21 +/- 1.79 micromol/g; CER + raxofelast = 15.71 +/- 2.14 micronol/g; p < 0.001), and reduced acinar cell damage evaluated by means of histology and serum levels of both amylase (CER + DMSO = 4063 +/- 707.9 U/l; CER + raxofelast = 1198 +/- 214.4 U/l; p < 0.001), and lipase (CER + DMSO = 1654 +/- 330 U/l; CER + raxofelast = 386 +/- 118.2 U/l; p < 0.001), Furthermore, raxofelast reduced pancreatic NF-kappaB activation and the TNF-alpha mRNA levels and tissue content of mature protein in the pancreas. Indeed, lipid peroxidation inhibition might be considered a potential therapeutic approach to prevent the severe damage in acute pancreatitis.
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PMID:Lipid peroxidation inhibition reduces NF-kappaB activation and attenuates cerulein-induced pancreatitis. 1274 37

Although oxygen free radicals (OFR) are considered to be one of the pathophysiological mechanisms involved in acute pancreatitis (AP), the contribution of acinar cells to their production is not well established. The aim of the present study was to determine the effect of N-acetylcysteine (NAC) in the course of AP induced by pancreatic duct obstruction (PDO) in rats, directly analysing by flow cytometry the quantity of OFR generated in acinar cells. NAC (50 mg/kg) was administered 1 h before and 1 h after PDO. Measurements by flow cytometry of OFR generated in acinar cells were taken at different PDO times over 24 h, using dihydrorhodamine-123 as fluorescent dye. Histological studies of pancreas and measurements of neutrophil infiltration in the pancreas, pancreatic glutathione (GSH), malondialdehyde (MDA) levels, plasma amylase activity and hemoconcentration were carried out in order to assess the severity of AP at different stages. NAC effectively blunted GSH depletion at early AP stages and prevented OFR generation found in acinar cells as a consequence of AP induced by PDO. This attenuation of the redox state impairment reduced cellular oxidative damage, as reflected by less severe pancreatic lesions, normal pancreatic MDA levels, as well as diminished neutrophil infiltration in pancreas. Hyperamylasemia and hemoconcentration following AP induction were ameliorated by NAC administration at early stages, when oxidative stress seems to be critical in the development of pancreatitis. In conclusion, NAC reinforces the antioxidant defences in acinar cells, preventing OFR generation therefore attenuating oxidative damage and subsequently reducing the severity of PDO-induced AP at early stages of the disease.
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PMID:N-acetylcysteine prevents intra-acinar oxygen free radical production in pancreatic duct obstruction-induced acute pancreatitis. 1463 49

Although the role of oxidative stress in acute pancreatitis (AP) has been studied in several animal models, little data are available regarding AP induced by pancreatic duct obstruction. We characterized the protective effects of melatonin on pancreaticobiliary inflammation and associated remote organ injury. In Sprague-Dawley rats, either the common pancreaticobiliary duct (PBDL; n = 28) or bile duct (BDL; n = 28) was ligated or a sham operation was applied (n = 14). Either melatonin (10 mg/kg) or vehicle (saline; 1 mL/kg) was administered intraperitoneally (i.p.) immediately before the surgery and twice a day until the rats were decapitated at 6 or 72 h. The pancreas, liver, kidneys and lungs were removed and tissue samples were stored for the determination of malondialdehyde (MDA) and glutathione (GSH) levels and myelopreoxidase activity. The results demonstrate that pathogenesis of acute obstructive pancreatitis involves not only the oxidative damage of the pancreatic and hepatic tissues, as assessed by increased MDA and reduced GSH levels, but the lungs and kidneys are also challenged by oxidant injury. Similarly, hepatic oxidative injury caused by cholestasis was also accompanied by pulmonary, renal and even pancreatic damage. The biochemical findings were also verified histologically. Melatonin, probably because of its free-radical scavenging and antioxidant activity, which involves an inhibitory effect on tissue neutrophil infiltration, protected all the affected tissues.
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PMID:Melatonin protects against pancreaticobiliary inflammation and associated remote organ injury in rats: role of neutrophils. 1548 53

The purpose of this study is to analyze the protective effect of combining N-acetylcysteine (NAC) and hyberbaric oxygen (HBO) treatment in the lung tissue during acute pancreatitis. Sixty Sprague-Dawley male rats were randomly divided into five groups; Group I; Control group (n=12), Group II; pancreatitis group (n=12), Group III; pancreatitis + NAC treatment group (n=12), Group IV; pancreatitis + HBO treatment group (n=12), Group V; pancreatitis + HBO + NAC treatment group (n=12). HBO was applied postoperatively for 5 days, twice a day at 2.5 fold absolute atmospheric pressure for 90 min. Lung tissue was obtained for measuring malondialdehyde (MDA), superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GSH-Px) levels along with histopathological tissue examinations. This study showed that all three treated groups (HBO alone, NAC alone and combined HBO+NAC treatment) had pulmonary protective effects during acute necrotizing pancreatitis.
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PMID:Pulmonary protective effects of hyberbaric oxygen and N-acetylcysteine treatment in necrotizing pancreatitis. 1608 13

The cell-permeant MG132 tripeptide (Z-Leu-Leu-Leu-aldehyde) is a peptide aldehyde proteasome inhibitor that also inhibits other proteases, including calpains and cathepsins. By blocking the proteasome, this tripeptide has been shown to induce the expression of cell-protective heat shock proteins (HSPs) in vitro. Effects of MG132 were studied in an in vivo model of acute pancreatitis. Pancreatitis was induced in male Wistar rats by injecting 2 x 100 microug/kg cholecystokinin octapeptide intraperitoneally (ip) at an interval of 1 h. Pretreating the animals with 10 mg/kg MG132 ip before the induction of pancreatitis significantly inhibited IkappaB degradation and subsequent activation of nuclear factor-kappaB (NF-kappaB). MG132 also increased HSP72 expression. Induction of HSP72 and inhibition of NF-kappaB improved parameters of acute pancreatitis. Thus MG132 significantly decreased serum amylase, pancreatic weight/body weight ratio, pancreatic myeloperoxidase activity, proinflammatory cytokine concentrations, and the expression of pancreatitis-associated protein. Parameters of oxidative stress (GSH, MDA, SOD, etc.) were improved in both the serum and the pancreas. Histopathological examinations revealed that pancreatic specimens of animals pretreated with the peptide demonstrated milder edema, cellular damage, and inflammatory activity. Our findings show that simultaneous inhibition of calpains, cathepsins, and the proteasome with MG132 prevents the onset of acute pancreatitis.
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PMID:The proteasome inhibitor MG132 protects against acute pancreatitis. 1621 30

Black Tea Extract (BTE), a phytocompound has been attributed with a plethora of health-promoting actions. We have previously demonstrated that BTE inhibits chronic hepatitis in a rat model induced with high-fat and ethanol (EtOH). This study reports that BTE prevents altered pancreatic acinar cell functions, oxidative stress, inflammatory changes and DNA damage in the EtOH+cholecystokinin (CCK)-induced model of pancreatitis. The EtOH+CCK model rats were administered with BTE, and were examined the activity of pancreatic digestive enzymes (amylase and lipase), proinflammatory cytokines (IL-6 and TNF-alpha), oxidative and antioxidative enzymes (nitric oxide, NO; malondialdehyde, MDA; superoxide dismutase, SOD; catalase, CAT), antioxidant level (glutathione, GSH), histopathological changes and the integrity of genomic DNA. Results show that because of chronic EtOH treatment, serum level of amylase and lipase (two biomarkers for pancreatitis) and pancreatic levels of MDA and NO (two biomarkers of oxidative stress) increased significantly, which could be effectively blunted by BTE. BTE could normalize EtOH+CCK-induced suppressed activities of SOD and CAT, and GSH content of pancreatic tissue. Also, histopathological and inflammatory changes during EtOH+CCK-induced pancreatitis could be blunted by BTE. Furthermore, BTE could effectively reduce EtOH+CCK-induced increase in DNA fragmentation and damage. These findings suggest that BTE prevents pancreatitis caused by chronic EtOH+CCK toxicity presumably by enhancing antioxidant, anti-inflammatory and antiapoptotic activity in rats.
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PMID:Aqueous extract of black tea (Camellia sinensis) prevents ethanol+cholecystokinin-induced pancreatitis in a rat model. 1628 61


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