Role of oxidative stress in the pathogenesis of caerulein-induced acute pancreatitis

Dâbrowski, A; Konturek, Stanisław J.; Konturek, J. W.; Gabryelewicz, A

doi:10.1016/s0014-2999(99)00421-5

Cited by 113 publications

(101 citation statements)

References 52 publications

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“…In AP, there is an excessive production of ROS due to the activation of leukocytes and the formation of proinflammatory interleukins (25). Several studies have reported an increase in MDA levels and a decrease in the activity of antioxidant enzymes (11,(22)(23)(24). In the present study, we observed higher tissue MDA levels and lower CAT and GPx enzyme activity levels in the cerulein group than in the control group.…”

Section: Resultssupporting

confidence: 68%

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Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

Batçıoğlu

Gül

Uyumlu

et al. 2009

Braz J Med Biol Res

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The aim of this study was to evaluate the role of oxidative damage in pancreatitis-induced hepatic injury. Thirty-five rats were divided into five groups (each of 7 rats): control, cerulein (100 µg/kg body weight), cerulein and pentoxifylline (12 mg/kg body weight), cerulein plus L-NAME (10 mg/kg body weight) and cerulein plus L-arginine (160 mg/kg body weight). The degree of hepatic cell degeneration differed significantly between groups. Mean malondialdehyde levels were 7.00 ± 2.29, 20.89 ± 10.13, 11.52 ± 4.60, 18.69 ± 8.56, and 8.58 ± 3.68 nmol/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Mean catalase activity was 3.20 ± 0.83, 1.09 ± 0.35, 2.05 ± 0.91, 1.70 ± 0.60, and 2.85 ± 0.47 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively, and mean glutathione peroxidase activity was 0.72 ± 0.25, 0.33 ± 0.09, 0.37 ± 0.04, 0.34 ± 0.07 and 0.42 ± 0.1 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Cerulein-induced liver damage was accompanied by a significant increase in tis sue malondialdehyde levels (P < 0.05) and a significant decrease in catalase (P < 0.05) and GPx activities (P < 0.05). L-arginine and pentoxifylline, but not L-NAME, protected against this damage. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancre atitis-induced hepatic damage.

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Section: Resultssupporting

confidence: 68%

“…While the mechanism of AP is not fully known, it is believed that reactive oxygen species (ROS) play a major role in the pathogenesis of AP (21,22). Acinar cells have been shown to produce large amounts of ROS in the early stages of AP in rats (23).…”

Section: Resultsmentioning

confidence: 99%

Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

Batçıoğlu

Gül

Uyumlu

et al. 2009

Braz J Med Biol Res

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“…Elevations of cytosolic Ca 2 + , which can locally reach low micromolar concentrations (as shown in experimental pancreatitis), are believed to mediate trypsinogen activation and other pathological responses of pancreatitis (70,74). Oxidative stress is also implicated in the pathogenesis of pancreatitis; however, the roles of ROS and the targets of ROS in the acinar cell have not been elucidated (14,18,46). Both Ca 2 + and ROS are major inducers of MMP, leading to cell death in other organs (24,44).…”

Section: Bcl-2 Proteins Are Key Regulators Of Mitochondrial Permeabilmentioning

confidence: 99%

Organellar Dysfunction in the Pathogenesis of Pancreatitis

Gukovsky

Pandol

Gukovskaya

2011

Antioxidants & Redox Signaling

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Significance: Acute pancreatitis is an inflammatory disease of exocrine pancreas that carries considerable morbidity and mortality; its pathophysiology remains poorly understood. During the past decade, new insights have been gained into signaling pathways and molecules that mediate the inflammatory response of pancreatitis and death of acinar cells (the main exocrine pancreas cell type). By contrast, much less is known about the acinar cell organellar damage in pancreatitis and how it contributes to the disease pathogenesis. Recent Advances: This review summarizes recent findings from our group, obtained on experimental in vivo and ex vivo models, which reveal disordering of key cellular organelles, namely, mitochondria, autophagosomes, and lysosomes, in pancreatitis. Our results indicate a critical role for mitochondrial permeabilization in determining the balance between apoptosis and necrosis in pancreatitis, and thus the disease severity. We further investigate how the mitochondrial dysfunction (and hence acinar cell death) is regulated by Ca 2+ , reactive oxygen species, and BclxL, in relation to specific properties of pancreatic mitochondria. Our results also reveal that autophagy, the principal cellular degradative, lysosome-driven pathway, is impaired in pancreatitis due to inefficient lysosomal function, and that impaired autophagy mediates two key pathological responses of pancreatitis-accumulation of vacuoles in acinar cells and the abnormal, intra-acinar activation of digestive enzymes such as trypsinogen. Critical Issues and Future Directions: The findings discussed in this review indicate critical roles for mitochondrial and autophagic/lysosomal dysfunctions in the pathogenesis of pancreatitis and delineate directions for detailed investigations into the molecular events that underlie acinar cell organellar damage. Antioxid. Redox Signal. 15, 2699-2710.

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“…Actived macrophages release pro-inflammatory cytokines in response to the local damage of the pancreas. Moreover, increased oxidative stress appeared during pancreatitis in the course of AP (Dabrowski et al, 1999;Telek et al, 1999;Abu-Zidan et al, 2000;Shi et al, 2005). At present there are evidences of a synergy or the relationship between oxidative stress and pro-inflammatory cytokines in development of the inflammatory response in AP Pereda et al, 2006).…”

Section: Introductionmentioning

confidence: 95%

The Combined Effects of Etanercept Plus Methylprednisolone on Pancreatic Oxidative Stress in Acute Pancreatitis Induced by Cerulein

Günay¹,

Kılıç²,

AMANVERMEZ³

2011

jecm

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KeywordsEtanercept Methylprednisolone Acute pancreatitis Oxidative stress Malondialdehyde Protein carbonyls ARTICLE INFO ABSTRACTWhether etanercept plus metylprednisolone reduce pancreatic oxidative stress and injury during pancreatitis is unknown well. The aim of this study was to examine the therapeutic effects of etanercept and methylprednisolone (MP) on acute pancreatitis and oxidative stress in acute pancreatitis (AP) induced by cerulein in a rat model. The study was performed with 48 rats divided into 6 groups (n = 8/group): 1-sham, 2-cerulein-induced pancreatitis (over 10 hours), 3-cerulein-pancreatitis (over 20 hours), 4-etanercept (5 mg/ kg, i.p.), 5-methylprednisolone (10 mg/kg, i.m.), 6-etanercept plus methylprednisolone. Also, the rats in groups 4, 5, and 6 were cerulein-induced pancreatitis at 20 hours. After the treatment, the pancreas and blood were taken for histopathological and biochemical analysis. All cerulein-treated rats developed biochemical and pathological acute pancreatitis after 10-20 hours. The markers of oxidative stress such as protein carbonyls, lipid peroxidation, and myeloperoxidase (mpo) in the pancreas tissues were increased in the group 2 and 3, but these were lower in etanercept and MP-treated rats compared to groups 3. Pancreatic mpo activity was considerably reduced in pancreas tissues at 20 h after the administration of etanercept plus metylprednisolone in the group 6 compared to group 3. In AP induced by cerulein, the treatment of etanercept plus methylprednisolone may ameliorate pancreatic oxidative stress in rats.

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Role of oxidative stress in the pathogenesis of caerulein-induced acute pancreatitis

Cited by 113 publications

References 52 publications

Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

Organellar Dysfunction in the Pathogenesis of Pancreatitis

The Combined Effects of Etanercept Plus Methylprednisolone on Pancreatic Oxidative Stress in Acute Pancreatitis Induced by Cerulein

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