Oxidative stress: an important phenomenon with pathogenetic significance in the progression of acute pancreatitis

Tsai, Kelvin K.; Wang, S. S.; Chen, Tyng-Guey; Kong, Chi Woon; Chang, Full‐Young; Lee, Shou‐Dong; Lu, Fung Jou

doi:10.1136/gut.42.6.850

Cited by 145 publications

(120 citation statements)

References 35 publications

(28 reference statements)

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“…This results in edema, vascular damage, hemorrhage and cell death (18,19). In addition to oxidative stress (20) and calcium overload (21), hypotension (22) and low acinar pH (23) contribute to these initiation processes. After initial production of active pancreatic enzymes, local cell death and systemic inflammation ensue.…”

Section: Introductionmentioning

confidence: 99%

Cell Death and DAMPs in Acute Pancreatitis

Kang

Lotze

Zeh

et al. 2014

Mol Med

124

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The pancreas is a dual-purpose gland with exocrine and endocrine functions. The exocrine pancreas produces digestive proteases in inactive proenzyme form, namely zymogens. The pancreas is normally able to protect itself from zymogen activation by synthesis of protease inhibitors such as pancreatic secretory trypsin inhibitor and serine protease inhibitor (for example, SPINK1/Spink3). By contrast, pancreatic autodigestion and subsequent AP is initiated once these defenses are impaired. In studies of rodent models (for example, repetitive cerulein or L-arginine injections, choline-deficient ethionine supplementation [CDE] diet, perfusion of taurocholate into the biliary or pancreatic duct and surgical ligation or infusion of pancreatic duct models), some essential pathogenic AP events have been identified (see Figure 1) (15,16).The development of AP involves a complex cascade of events (17), which start with injury or disruption of the pan- Cell Death and DAMPs in Acute PancreatitisRui Kang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, and Daolin Tang Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP . Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP . DAMPs might be an attractive therapeutic target in AP.

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Section: Introductionmentioning

confidence: 99%

Cell Death and DAMPs in Acute Pancreatitis

Kang

Lotze

Zeh

et al. 2014

Mol Med

124

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“…Clinical studies have shown that OS is higher in patients with AP than in healthy volunteers or patients with acute abdominal processes other than AP (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), and in patients with severe AP (SAP) it is higher than in those with mild AP (MAP) (8)(9)(10)(11)(12)(13)(14)16,17).…”

Section: Introductionmentioning

confidence: 99%

Malondialdehyde in early phase of acute pancreatitis

Hernández

Miranda

Pascual

et al. 2011

Rev. esp. enferm. dig.

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Aims: to assess oxidative stress in acute pancreatitis, its evolution over time and its relationship with the severity of the disease.Methods: during a two-year period, patients with acute pancreatitis with less than 24 hours of pain were evaluated. Serum was obtained the first, second and fourth day from admittance, if complications were detected, and after recovery. Malondialdehyde was determined by high performance liquid chromatography. Twenty healthy volunteers constituted the control group. Malondialdehyde between groups was compared with Mann-Whitney and KruskalWallis tests; malondialdehyde evolution was studied with Wilcoxon test.Results: one hundred and sixty-nine patients were included (91 women, median age 67 years, range 20-95); 33 suffered a severe episode. Malondialdehyde decreased from first to fourth day (0.600 vs. 0.451 vs. 0.343 M, respectively, p < 0.05). When complications were detected, malondialdehyde level was similar to that of first and second day (0.473 M, p > 0.05). In severe attacks malondialdehyde was higher than in control group at day 2 (severe: 0.514; mild: 0.440; control: 0.347 M, p < 0.05 severe vs. control).Conclusions: an early oxidative stress is observed in acute pancreatitis. In severe attacks, oxidative stress remains high longer than in mild episodes. The onset of complications is associated with high malondialdehyde concentration.

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“…Oxidative stress has been implicated in the development of acute pancreatitis in diverse animal experimental models, including fatty acid infusion, ischaemia, pancreatic duct obstruction, gallstone pancreatitis and alcohol ingestion, 60,[62][63][64] and measured in patients with mild and severe acute pancreatitis. 65 Previously, we have demonstrated the vital role of Ca 2 þ on MPTP opening in pancreatic acinar cell apoptosis induced by the oxidant menadione. 10 Crucially, the Ca 2 þ chelator BAPTA prevented both menadione-induced repetitive cytosolic Ca 2 þ spikes and apoptosis, instigated via the intrinsic apoptotic pathway.…”

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confidence: 98%