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Zhang H, Xiang X, Wang C, Li T, Xiao X, He L. Different effects of acute and chronic oxidative stress on the intestinal flora and gut-liver axis in weaned piglets. Front Microbiol 2024; 15:1414486. [PMID: 38952442 PMCID: PMC11215049 DOI: 10.3389/fmicb.2024.1414486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 06/04/2024] [Indexed: 07/03/2024] Open
Abstract
Introduction Oxidative stress plays a pivotal role in modulating the balance of intestinal flora and the gut-liver axis, while also serving as a key determinant of the growth potential of weaned piglets. However, few studies have subdivided and compared acute and chronic oxidative stress. Methods In this study, an intestinal model of acute oxidative stress in weaned piglets using paraquat (PQ) and a chronic oxidative stress model using D-galactosa in weaned piglets were conducted. And we further systematically compare their effects. Results Both acute and chronic oxidative stress models impaired intestinal barrier function and liver function. Chronic stress caused by D-galactose can result in severe redox dysregulation, while acute stress caused by paraquat can lead to inflammation and liver damage. Additionally, the components involved in the CAR pathway were expressed differently. Chronic or acute oxidative stress can reduce the diversity and composition of intestinal flora. In the PQ group, the richness of Mogibacterium and Denitratisoma improved, but in the D-gal group, the richness of Catenisphaera and Syntrophococcus increased. Discussion Not only does this research deepen our understanding of the effects of acute and chronic oxidative stress on intestinal functions, but it also characterizes characteristic changes in the gut flora, potentially identifying novel therapeutic targets and opening new avenues for future research.
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Affiliation(s)
- Hongyu Zhang
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), Changsha, China
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Laboratory of Animal Nutrition and Hunan Health, College of Life Sciences, Hunan Normal University, Changsha, China
| | - Xuan Xiang
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Chenyu Wang
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Laboratory of Animal Nutrition and Hunan Health, College of Life Sciences, Hunan Normal University, Changsha, China
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Tiejun Li
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Xuping Xiao
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), Changsha, China
| | - Liuqin He
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Laboratory of Animal Nutrition and Hunan Health, College of Life Sciences, Hunan Normal University, Changsha, China
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
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Tao J, Zhang Y, Huang Y, Xu M. The role of iron and ferroptosis in the pathogenesis of acute pancreatitis. J Histotechnol 2023; 46:184-193. [PMID: 37823564 DOI: 10.1080/01478885.2023.2261093] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 09/12/2023] [Indexed: 10/13/2023]
Abstract
Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Iron is an essential element for life and is involved in many metabolic processes. Ferroptosis is a type of regulated cell death that is triggered by iron and oxidative stress. A well-established mouse AP model was adopted to study the role of iron and ferroptosis in the pathogenesis of pancreatitis. Mice were injected with cerulein to induce AP, and pancreatic tissue samples were analyzed to determine the pathology, cell death, iron deposition, expression of iron transporters, and lipid peroxidation. The role of iron was studied by giving mice extra iron or iron chelator. In vitro studies with acinar cells with ferroptosis activator and inhibitor were also performed to assess the inflammatory response. Iron was found accumulated in the pancreatic tissue of mice who suffered cerulein-induced pancreatitis. Cell death and lipid peroxidation increased in these tissues and could be further modulated by iron dextran or iron chelator. Mice given Hemin through gavage had reduced levels of GSH in pancreatic tissue and increased inflammatory response. Studies with acinar cells showed increased levels of lipid peroxidation and ferroptosis-specific mitochondrial damage when treated with ferroptosis inducer and inflammatory cytokines.
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Affiliation(s)
- Jin Tao
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yiyi Zhang
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yinshi Huang
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Xu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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3
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He H, Long M, Duan Y, Gu N. Prussian blue nanozymes: progress, challenges, and opportunities. NANOSCALE 2023; 15:12818-12839. [PMID: 37496423 DOI: 10.1039/d3nr01741a] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
Abstract
Prussian Blue Nanozymes (PBNZs) have emerged as highly efficient agents for reactive oxygen species (ROS) elimination, owing to their multiple enzyme-like properties encompassing catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activities. As a functional nanomaterial mimicking enzyme, PBNZs not only surmount the limitations of natural enzymes, such as instability and high manufacturing costs, but also exhibit superior stability, tunable activity, low storage expenses, and remarkable reusability. Consequently, PBNZs have gained significant attention in diverse biomedical applications, including disease diagnosis and therapy. Over the past decade, propelled by advancements in catalysis science, biotechnology, computational science, and nanotechnology, PBNZs have witnessed remarkable progress in the exploration of their enzymatic activities, elucidation of catalytic mechanisms, and wide-ranging applications. This comprehensive review aims to provide a systematic overview of the discovery and catalytic mechanisms of PBNZ, along with the strategies employed to modulate their multiple enzyme-like activities. Furthermore, we extensively survey the recent advancements in utilizing PBNZs for scavenging ROS in various biomedical applications. Lastly, we analyze the existing challenges of translating PBNZs into therapeutic agents for clinical use and outline future research directions in this field. By presenting a comprehensive synopsis of the current state of knowledge, this review seeks to contribute to a deeper understanding of the immense potential of PBNZs as an innovative therapeutic agent in biomedicine.
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Affiliation(s)
- Hongliang He
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, People's Republic of China
| | - Mengmeng Long
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, People's Republic of China
| | - Yifan Duan
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, People's Republic of China
| | - Ning Gu
- School of Medicine, Nanjing University, Nanjing, 210093, People's Republic of China.
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4
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Pădureanu V, Florescu DN, Pădureanu R, Ghenea AE, Gheonea DI, Oancea CN. Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review). Exp Ther Med 2022; 23:197. [PMID: 35126700 PMCID: PMC8794551 DOI: 10.3892/etm.2022.11120] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 10/29/2021] [Indexed: 11/06/2022] Open
Abstract
Acute pancreatitis (AP) is a severe disease with a high prevalence and 3 to 15% mortality worldwide, which can represent an important challenge for the physician. Oxidative stress and antioxidants are involved in AP progression. The mechanisms responsible for the onset and progression of AP are still poorly understood. Previous studies have highlighted the important contribution of antioxidants and oxidative stress in AP. The existence of a relationship between oxidative stress and antioxidants in AP is unquestionable, although a more accurate understanding of the mechanistic pathways involved is required to create a solid basis for potential prevention or treatment strategies. Further investigation is needed to clarify the role of antioxidant status and the severity of AP and to determine the association between oxidative stress and pancreatic enzyme activities. Antioxidant therapy may represent an interesting option for the management of patients with AP, although additional information about the effectiveness of this potential treatment is required.
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Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan Nicolae Florescu
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, Emergency Clinical County Hospital of Craiova, 200642 Craiova, Romania
| | - Alice Elena Ghenea
- Department of Bacteriology-Virology-Parasitology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan Ionuț Gheonea
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Carmen Nicoleta Oancea
- Department of Analytical Chemistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Vobugari N, Kim J, Gandhi KD, Lee ZE, Smith HP. Iron-Storage Disorder Presenting as Chronic Diarrhea. Cureus 2021; 13:e18864. [PMID: 34804717 PMCID: PMC8598083 DOI: 10.7759/cureus.18864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2021] [Indexed: 11/15/2022] Open
Abstract
The involvement of the endocrine pancreas leading to bronze diabetes is well studied. However, little is known about the pathophysiology of iron dysregulation involving the exocrine pancreas. We present a unique association between the exocrine pancreas and iron dysregulation. A 45-year-old female presented with chronic diarrhea and low fecal elastase indicative of pancreatic exocrine dysfunction. MRI of the abdomen/pelvis showed iron deposition in the pancreas, suggesting an associated iron-storage disorder without features suggesting chronic pancreatitis. Association of an iron-storage disorder with pancreatic exocrine dysfunction has been reported only in one other case report. Pancreatic exocrine dysfunction can be directly associated with an iron-storage disorder that involves the pancreas. This should be included in the differential and diagnostic work-up of chronic diarrhea of unclear etiology. Based on the literature, we have highlighted the potential pathophysiology relevant to the case.
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Affiliation(s)
- Nikitha Vobugari
- Internal medicine, MedStar Washington Hospital Center, Washington, D.C., USA
| | - Jeffrey Kim
- Gastroenterology and Hepatology, MedStar Georgetown University Hospital, Washington, D.C., USA
| | - Kejal D Gandhi
- Internal Medicine, MedStar Washington Hospital Center, Washington, D.C., USA
| | - Zone-En Lee
- Gastroenterology and Hepatology, MedStar Georgetown University Hospital, Washington, D.C., USA
| | - Hedy P Smith
- Hematology and Medical Oncology, MedStar Washington Hospital Center, Washington, D.C., USA
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6
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Zhao Y, Schoeps B, Yao D, Zhang Z, Schuck K, Tissen V, Jäger C, Schlitter AM, van der Kammen R, Ludwig C, D'Haese JG, Raulefs S, Maeritz N, Shen S, Zou X, Krüger A, Kleeff J, Michalski CW, Friess H, Innocenti M, Kong B. mTORC1 and mTORC2 Converge on the Arp2/3 Complex to Promote Kras G12D-Induced Acinar-to-Ductal Metaplasia and Early Pancreatic Carcinogenesis. Gastroenterology 2021; 160:1755-1770.e17. [PMID: 33388318 DOI: 10.1053/j.gastro.2020.12.061] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 12/04/2020] [Accepted: 12/21/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Oncogenic KrasG12D induces neoplastic transformation of pancreatic acinar cells through acinar-to-ductal metaplasia (ADM), an actin-based morphogenetic process, and drives pancreatic ductal adenocarcinoma (PDAC). mTOR (mechanistic target of rapamycin kinase) complex 1 (mTORC1) and 2 (mTORC2) contain Rptor and Rictor, respectively, and are activated downstream of KrasG12D, thereby contributing to PDAC. Yet, whether and how mTORC1 and mTORC2 impact on ADM and the identity of the actin nucleator(s) mediating such actin rearrangements remain unknown. METHODS A mouse model of inflammation-accelerated KrasG12D-driven early pancreatic carcinogenesis was used. Rptor, Rictor, and Arpc4 (actin-related protein 2/3 complex subunit 4) were conditionally ablated in acinar cells to deactivate the function of mTORC1, mTORC2 and the actin-related protein (Arp) 2/3 complex, respectively. RESULTS We found that mTORC1 and mTORC2 are markedly activated in human and mouse ADM lesions, and cooperate to promote KrasG12D-driven ADM in mice and in vitro. They use the Arp2/3 complex as a common downstream effector to induce the remodeling the actin cytoskeleton leading to ADM. In particular, mTORC1 regulates the translation of Rac1 (Rac family small GTPase 1) and the Arp2/3-complex subunit Arp3, whereas mTORC2 activates the Arp2/3 complex by promoting Akt/Rac1 signaling. Consistently, genetic ablation of the Arp2/3 complex prevents KrasG12D-driven ADM in vivo. In acinar cells, the Arp2/3 complex and its actin-nucleation activity mediated the formation of a basolateral actin cortex, which is indispensable for ADM and pre-neoplastic transformation. CONCLUSIONS Here, we show that mTORC1 and mTORC2 attain a dual, yet nonredundant regulatory role in ADM and early pancreatic carcinogenesis by promoting Arp2/3 complex function. The role of Arp2/3 complex as a common effector of mTORC1 and mTORC2 fills the gap between oncogenic signals and actin dynamics underlying PDAC initiation.
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MESH Headings
- Acinar Cells/enzymology
- Acinar Cells/pathology
- Actin-Related Protein 2-3 Complex/genetics
- Actin-Related Protein 2-3 Complex/metabolism
- Animals
- Carcinoma, Pancreatic Ductal/enzymology
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/pathology
- Cell Transformation, Neoplastic/genetics
- Cell Transformation, Neoplastic/metabolism
- Cell Transformation, Neoplastic/pathology
- Disease Models, Animal
- Gene Expression Regulation, Neoplastic
- Humans
- Mechanistic Target of Rapamycin Complex 1/genetics
- Mechanistic Target of Rapamycin Complex 1/metabolism
- Mechanistic Target of Rapamycin Complex 2/genetics
- Mechanistic Target of Rapamycin Complex 2/metabolism
- Metaplasia
- Mice, Inbred C57BL
- Mice, Knockout
- Mutation
- Pancreatic Ducts/enzymology
- Pancreatic Ducts/pathology
- Pancreatic Neoplasms/enzymology
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/pathology
- Proto-Oncogene Proteins p21(ras)/genetics
- Rapamycin-Insensitive Companion of mTOR Protein/genetics
- Rapamycin-Insensitive Companion of mTOR Protein/metabolism
- Regulatory-Associated Protein of mTOR/genetics
- Regulatory-Associated Protein of mTOR/metabolism
- Signal Transduction
- Mice
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Affiliation(s)
- Yamin Zhao
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Benjamin Schoeps
- Institute of Molecular Immunology and Experimental Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Dianbo Yao
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Zhiheng Zhang
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Kathleen Schuck
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Vivien Tissen
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Carsten Jäger
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | | | - Rob van der Kammen
- Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Christina Ludwig
- Bavarian Center for Biomolecular Mass Spectrometry, Technical University of Munich, Freising, Germany
| | - Jan G D'Haese
- Department of General, Visceral, and Transplantation, Ludwig Maximilians University, Munich, Germany
| | - Susanne Raulefs
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Nadja Maeritz
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Shanshan Shen
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Xiaoping Zou
- Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
| | - Achim Krüger
- Institute of Molecular Immunology and Experimental Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Jörg Kleeff
- Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Germany
| | | | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Metello Innocenti
- Heidelberg University Biochemistry Center, Heidelberg University, Heidelberg, Germany
| | - Bo Kong
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China; German Cancer Consortium at the partner site Munich, Munich, Germany.
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7
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Mohta S, Singh N, Gunjan D, Kumar A, Saraya A. Systematic review and meta-analysis: Is there any role for antioxidant therapy for pain in chronic pancreatitis. JGH OPEN 2021; 5:329-336. [PMID: 33732878 PMCID: PMC7936613 DOI: 10.1002/jgh3.12433] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 09/29/2020] [Accepted: 10/04/2020] [Indexed: 12/19/2022]
Abstract
Chronic pancreatitis (CP) is an irreversible disease with increased oxidative stress. The therapeutic role of antioxidants for pain reduction in CP is debatable. A systematic review of articles in PubMed and Embase until February 2020 was performed. Only randomized controlled trials conducted on humans to evaluate the therapeutic effects of antioxidants for pain in CP were included. Studies of other design, nonhuman studies, and those that did not objectively assess pain were excluded. Twelve articles and four articles were eligible for qualitative and quantitative analysis, respectively. The four included studies had a total of 352 participants. Pain reduction as measured by a visual analog scale was not significantly different in the antioxidant group compared to placebo (standardized mean difference = -0.14 [95% confidence interval [CI] = -0.44 to 0.17]; P = 0.38). Number of pain-free participants was also similar (odds ratio [OR] = 1.59 [0.97-2.59]; P = 0.06). There was no difference in outcome when comparing different etiologies of CP or age group. The reduction in the number of analgesics used did not differ between both groups. Antioxidants were not associated with increased adverse events (OR = 2.59 [CI = 0.77-8.69]; P = 0.12). A qualitative analysis on the effect on quality of life did not suggest any significant improvement with antioxidants. There was no significant pain reduction or change in quality of life in CP patients with use of antioxidants. This makes their routine use in the management of CP questionable. However, further studies may identify a subgroup where they are more useful.
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Affiliation(s)
- Srikant Mohta
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Namrata Singh
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Deepak Gunjan
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
| | - Amit Kumar
- Department of Neurology All India Institute of Medical Sciences New Delhi India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition Unit All India Institute of Medical Sciences New Delhi India
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Superoxide Dismutase Predicts Persistent Circulation Failure and Mortality in the Early Stage of Acute Pancreatitis. Dig Dis Sci 2020; 65:3551-3557. [PMID: 31997054 DOI: 10.1007/s10620-020-06069-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 01/11/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Oxidative stress is an important event in the pathogenesis of acute pancreatitis. Superoxide dismutase is a major antioxidant enzyme in the body. The aim of this study was to investigate the changes in superoxide dismutase activity early in the onset of acute pancreatitis and its value in predicting the risk of organ failure and mortality. METHODS Data for 2549 patients hospitalized from 2013 to 2017 were extracted from the prospective database, and we selected 854 adult patients who were admitted within 24 h of disease onset with complete data. Serum superoxide dismutase activities on the first, second, and third days of hospital admission for patients with different severities, organ failure, and mortality were compared. The areas under the curve for the prediction of organ failure, pancreatic necrosis, and mortality were estimated using receiver operating characteristic curves. RESULTS Among the 854 adult patients, superoxide dismutase activities were significantly different among patients with mild acute pancreatitis, moderately severe acute pancreatitis, and severe acute pancreatitis (P = 0.005). Superoxide dismutase activity was significantly decreased in patients with persistent renal failure (77.8 ± 37.2), persistent circulatory failure (66.2 ± 14.9), and mortality (64.3 ± 16.0). The accuracy of superoxide dismutase with regard to predicting persistent circulatory failure and mortality was high, and the areas under the receiver operating characteristic curves were 0.83 and 0.84, respectively. CONCLUSIONS Superoxide dismutase activity was negatively correlated with the severity and clinical outcome of AP. Superoxide dismutase activity is highly accurate at predicting persistent circulation failure and mortality in the early stage of AP.
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9
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Kimita W, Petrov MS. Iron metabolism and the exocrine pancreas. Clin Chim Acta 2020; 511:167-176. [PMID: 33058846 DOI: 10.1016/j.cca.2020.10.013] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 10/06/2020] [Accepted: 10/08/2020] [Indexed: 12/18/2022]
Abstract
Although the pathophysiological mechanisms and consequences of gross derangements in iron metabolism are well known, little is known about the pathophysiological mechanisms underlying mild-to-moderate alterations in iron metabolism and their consequences. Growing evidence indicates that the exocrine pancreas has a bidirectional relationship with iron metabolism. Studies have shown alterations in circulating markers of iron metabolism, iron absorption, and intra-pancreatic iron deposition in pancreatitis. At the same time, exocrine pancreatic dysfunction has been shown in iron overload disorders. These observations reveal a compelling connection between the exocrine pancreas and iron metabolism, which are further elucidated by observations of therapeutic benefits of iron chelating agents and pancreatic enzyme replacement therapy. While the pancreas is not a major reservoir of iron in the body, better understanding of its relationship with iron metabolism may yield unexpected insights.
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Affiliation(s)
- Wandia Kimita
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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10
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Affiliation(s)
- Maxim S. Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand
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11
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Merry TL, Petrov MS. The rise of genetically engineered mouse models of pancreatitis: A review of literature. Biomol Concepts 2018; 9:103-114. [DOI: 10.1515/bmc-2018-0011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 10/19/2018] [Indexed: 12/15/2022] Open
Abstract
AbstractPancreatitis is increasingly recognized as not merely a local inflammation of the pancreas but also a disease with high frequency of systemic sequelae. Current understanding of the cellular mechanisms that trigger it and affect the development of sequelae are limited. Genetically engineered mouse models can be a useful tool to study the pathophysiology of pancreatitis. This article gives an overview of the genetically engineered mouse models that spontaneously develop pancreatitis and discusses those that most closely replicate different pancreatitis hallmarks observed in humans.
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Affiliation(s)
- Troy L. Merry
- Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand
- Discipline of Nutrition, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Maxim S. Petrov
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
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12
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The Use of International Classification of Diseases Codes to Identify Patients with Pancreatitis: A Systematic Review and Meta-analysis of Diagnostic Accuracy Studies. Clin Transl Gastroenterol 2018; 9:191. [PMID: 30287807 PMCID: PMC6172207 DOI: 10.1038/s41424-018-0060-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Accepted: 09/06/2018] [Indexed: 02/06/2023] Open
Abstract
Background Hospital discharge codes are increasingly used in gastroenterology research, but their accuracy in the setting of acute pancreatitis (AP) and chronic pancreatitis (CP), one of the most frequent digestive diseases, has never been assessed systematically. The aim was to conduct a systematic literature review and determine accuracy of diagnostic codes for AP and CP, as well as the effect of covariates. Methods Three databases (Pubmed, EMBASE and Scopus) were searched by two independent reviewers for relevant studies that used International Classification of Disease (ICD) codes. Summary estimates of sensitivity, specificity and positive predictive value were obtained from bivariate random-effects regression models. Sensitivity and subgroup analyses according to recurrence of AP and age of the study population were performed. Results A total of 24 cohorts encompassing 18,106 patients were included. The pooled estimates of sensitivity and specificity of ICD codes for AP were 0.85 and 0.96, respectively. The pooled estimates of sensitivity and specificity of ICD codes for CP were 0.75 and 0.94, respectively. The positive predictive value of ICD codes was 0.71 for either AP or CP. It increased to 0.78 when applied to incident episode of AP only. The positive predictive value decreased to 0.68 when the ICD codes were applied to paediatric patients. Conclusion Nearly three out of ten patients are misidentified as having either AP or CP with the indiscriminate use of ICD codes. Limiting the use of ICD codes to adult patients with incident episode of AP may improve identification of patients with pancreatitis in administrative databases.
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13
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CFTR Deletion Confers Mitochondrial Dysfunction and Disrupts Lipid Homeostasis in Intestinal Epithelial Cells. Nutrients 2018; 10:nu10070836. [PMID: 29954133 PMCID: PMC6073936 DOI: 10.3390/nu10070836] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Revised: 06/23/2018] [Accepted: 06/25/2018] [Indexed: 02/07/2023] Open
Abstract
Background: Cystic Fibrosis (CF) is a genetic disease in which the intestine exhibits oxidative and inflammatory markers. As mitochondria are the central source and the main target of reactive oxygen species, we hypothesized that cystic fibrosis transmembrane conductance regulator (CFTR) defect leads to the disruption of cellular lipid homeostasis, which contributes to mitochondrial dysfunction. Methods. Mitochondrial functions and lipid metabolism were investigated in Caco-2/15 cells with CFTR knockout (CFTR-/-) engineered by the zinc finger nuclease technique. Experiments were performed under basal conditions and after the addition of the pro-oxidant iron-ascorbate (Fe/Asc) complex. Results. Mitochondria of intestinal cells with CFTR-/-, spontaneously showed an altered redox homeostasis characterised by a significant decrease in the expression of PPARα and nuclear factor like 2. Consistent with these observations, 8-oxoguanine-DNA glycosylase, responsible for repair of ROS-induced DNA lesion, was weakly expressed in CFTR-/- cells. Moreover, disturbed fatty acid β-oxidation process was evidenced by the reduced expression of CPT1 and acyl-CoA dehydrogenase long-chain in CFTR-/- cells. The decline of mitochondrial cytochrome c and B-cell lymphoma 2 expression pointing to magnified apoptosis. Mitochondrial respiration was also affected as demonstrated by the low expression of respiratory oxidative phosphorylation (OXPHOS) complexes and a high adenosine diphosphate/adenosine triphosphate ratio. In contrast, the FAS and ACC enzymes were markedly increased, thereby indicating lipogenesis stimulation. This was associated with an augmented secretion of lipids, lipoproteins and apolipoproteins in CFTR-/- cells. The addition of Fe/Asc worsened while butylated hydroxy toluene partially improved these processes. Conclusions: CFTR silencing results in lipid homeostasis disruption and mitochondrial dysfunction in intestinal epithelial cells. Further investigation is needed to elucidate the mechanisms underlying the marked abnormalities in response to CFTR deletion.
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Cervantes A, Singh RG, Pendharkar SA, Bharmal SH, Petrov MS. Profile of Gut Hormones, Pancreatic Hormones and Pro-inflammatory Cytokines in New Zealand Maori. Gastroenterology Res 2018; 11:280-289. [PMID: 30116427 PMCID: PMC6089586 DOI: 10.14740/gr1042w] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 05/28/2018] [Indexed: 12/11/2022] Open
Abstract
Background Maori, indigenous people of New Zealand, have at least two times higher prevalence of obesity and diabetes in comparison with the general population in the country. Gut and pancreatic hormone profile differences as well as pro-inflammatory milieu may contribute to this disparity. The aim was to investigate the differences in gut hormones, pancreatic hormones and pro-inflammatory cytokines between Maori and non-Maori individuals. Methods This was a cross-sectional study. Fasting blood samples were collected to measure cholecystokinin, ghrelin, gastric inhibitory peptide, glicentin, glucagon-like peptide-1 and -2, oxyntomodulin, secretin, amylin, C-peptide, glucagon, insulin, pancreatic polypeptide, somatostatin, interleukin-6, monocyte chemoattractant protein-1 and tumour necrosis factor-α. Binary logistic regression analysis was conducted in one unadjusted and four adjusted statistical models adjusting for patient-, metabolic- and pancreatitis-related factors. Results A total of 8 Maori and 85 non-Maori individuals were included. Circulating levels of ghrelin, pancreatic polypeptide and interleukin-6 levels were significantly higher in Maori (P = 0.005, P = 0.003 and P = 0.011, respectively) in both unadjusted and all the four adjusted analyses. Other signaling molecules did not show consistently significant associations with ethnicity. Conclusion Profile of gut hormones, pancreatic hormones and pro-inflammatory cytokines appears to differ between Maori and non-Maori individuals, independent of obesity, diabetes and other covariates. This may go some way to explain the increased propensity to obesity and diabetes in the Maori population.
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Affiliation(s)
- Aya Cervantes
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Ruma G Singh
- School of Medicine, University of Auckland, Auckland, New Zealand
| | | | - Sakina H Bharmal
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand
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15
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Gillies NA, Pendharkar SA, Singh RG, Asrani VM, Petrov MS. Lipid metabolism in patients with chronic hyperglycemia after an episode of acute pancreatitis. Diabetes Metab Syndr 2017; 11 Suppl 1:S233-S241. [PMID: 28065464 DOI: 10.1016/j.dsx.2016.12.037] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 12/12/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND The importance of dyslipidemia is well recognized in the context of both risk factor for acute pancreatitis and prognostic factor for its in-hospital outcomes. With a growing appreciation of post-pancreatitis diabetes mellitus, there is a need to catalogue changes in lipid metabolism after hospitalization due to an acute pancreatitis attack and their associations with glucose metabolism. OBJECTIVE To investigate lipid metabolism in patients with impaired glucose homeostasis following acute pancreatitis. METHODS There were two study groups: newly diagnosed chronic hyperglycemia or normoglycemia after acute pancreatitis. During the fasting state, venous blood samples were collected to analyse markers of lipid metabolism (triglycerides, glycerol, low density lipoprotein, high density lipoprotein, total cholesterol, free fatty acids, and apolipoprotein-B) and glucose metabolism (HbA1c, insulin, index of adipose tissue insulin resistance (Adipo-IR), and HOMA-IR). Binary logistic and linear regression analyses were conducted, and potential confounders were adjusted for in multivariate analyses. RESULTS The study included 64 patients with normoglycemia and 19 - with chronic hyperglycemia. Glycerol was significantly associated with the development of chronic hyperglycemia in both unadjusted (p=0.02) and adjusted (p=0.006) models. Triglycerides were significantly associated with the development of chronic hyperglycemia in adjusted (p=0.019) model. Other markers of lipid metabolism did not differ significantly between the two groups. None of the markers of lipid metabolism was significantly associated with Adipo-IR or HOMA-IR. CONCLUSION Overall, patients with chronic hyperglycemia after acute pancreatitis appear to have a lipid profile indicative of an up-regulation of lipolysis, which is not significantly affected by either general or adipose tissue-specific insulin resistance.
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Affiliation(s)
| | | | - Ruma G Singh
- Department of Surgery, University of Auckland, New Zealand
| | | | - Maxim S Petrov
- Department of Surgery, University of Auckland, New Zealand.
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Soo DHE, Pendharkar SA, Jivanji CJ, Gillies NA, Windsor JA, Petrov MS. Derivation and validation of the prediabetes self-assessment screening score after acute pancreatitis (PERSEUS). Dig Liver Dis 2017; 49:1146-1154. [PMID: 28666861 DOI: 10.1016/j.dld.2017.05.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Revised: 05/21/2017] [Accepted: 05/22/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Approximately 40% of patients develop abnormal glucose metabolism after a single episode of acute pancreatitis. This study aimed to develop and validate a prediabetes self-assessment screening score for patients after acute pancreatitis. METHODS Data from non-overlapping training (n=82) and validation (n=80) cohorts were analysed. Univariate logistic and linear regression identified variables associated with prediabetes after acute pancreatitis. Multivariate logistic regression developed the score, ranging from 0 to 215. The area under the receiver-operating characteristic curve (AUROC), Hosmer-Lemeshow χ2 statistic, and calibration plots were used to assess model discrimination and calibration. The developed score was validated using data from the validation cohort. RESULTS The score had an AUROC of 0.88 (95% CI, 0.80-0.97) and Hosmer-Lemeshow χ2 statistic of 5.75 (p=0.676). Patients with a score of ≥75 had a 94.1% probability of having prediabetes, and were 29 times more likely to have prediabetes than those with a score of <75. The AUROC in the validation cohort was 0.81 (95% CI, 0.70-0.92) and the Hosmer-Lemeshow χ2 statistic was 5.50 (p=0.599). Model calibration of the score showed good calibration in both cohorts. CONCLUSION The developed and validated score, called PERSEUS, is the first instrument to identify individuals who are at high risk of developing abnormal glucose metabolism following an episode of acute pancreatitis.
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Affiliation(s)
- Danielle H E Soo
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | | | - Chirag J Jivanji
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Nicola A Gillies
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - John A Windsor
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Maxim S Petrov
- Department of Surgery, University of Auckland, Auckland, New Zealand.
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17
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Korc M, Jeon CY, Edderkaoui M, Pandol SJ, Petrov MS. Tobacco and alcohol as risk factors for pancreatic cancer. Best Pract Res Clin Gastroenterol 2017; 31:529-536. [PMID: 29195672 PMCID: PMC5747325 DOI: 10.1016/j.bpg.2017.09.001] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 08/25/2017] [Accepted: 09/03/2017] [Indexed: 02/07/2023]
Abstract
Pancreatic cancer is projected to become the leading cause of cancer deaths by 2050. The risk for pancreatic cancer may be reduced by up to 27% by modifying lifestyle risk factors, most notably tobacco smoking. Based on analysis of more than 2 million unselected individuals from general population, this article quantified the risk of pancreatic cancer in relation to lifelong tobacco smoking and alcohol consumption status, both alone and in combination. It also provided a state-of-the-art review of animal studies on the effect of tobacco smoke and alcohol on genetically engineered mouse models of pancreatic precursor lesions, as well as the role of immune microenvironment in pancreatic carcinogenesis activated by tobacco and alcohol.
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Affiliation(s)
- Murray Korc
- Departments of Medicine, Biochemistry and Molecular Biology, Indiana University School of Medicine, The Melvin and Bren Simon Cancer Center and the Pancreatic Cancer Signature Center, Indianapolis, USA
| | - Christie Y Jeon
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Mouad Edderkaoui
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Stephen J Pandol
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Maxim S Petrov
- Department of Surgery, University of Auckland, Auckland, New Zealand.
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Petrov MS. Diabetes of the exocrine pancreas: American Diabetes Association-compliant lexicon. Pancreatology 2017; 17:523-526. [PMID: 28655595 DOI: 10.1016/j.pan.2017.06.007] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 06/14/2017] [Accepted: 06/18/2017] [Indexed: 12/11/2022]
Abstract
Multidisciplinary teams, including gastroenterologists, endocrinologists, surgeons, dietitians, primary care physicians, and other health professionals, are involved in management of individuals with diabetes of the exocrine pancreas (DEP). This necessitates introduction of a uniform terminology to ensure proper communication and reporting. Because DEP is a form of secondary diabetes mellitus, it makes sense to align the evolving DEP lexicon with nomenclature and diagnostic standards advocated by a world leading professional body in the field of diabetes such as the American Diabetes Association. This Editorial offers a historical excursus on the terms used and proposes a new concise nomenclature and diagnostic criteria. This new taxonomy of DEP, compliant with the American Diabetes Association standards of diagnosis and care for patients with diabetes mellitus, will ensure standardisation of reporting in future clinical studies on DEP and enable a dynamic incorporation of glucose dysregulation mechanisms related specifically to diseases of the exocrine pancreas as new evidence emerges.
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Affiliation(s)
- Maxim S Petrov
- Department of Surgery, University of Auckland, Auckland, New Zealand.
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Rajapriya S, Geetha A, Ganesan Kripa K. A study on the GC-MS analysis of bioactive components and pancreato-protective effect of methanolic extract of Brassica oleracea L. var. botrytis. Nat Prod Res 2017; 31:2174-2177. [DOI: 10.1080/14786419.2017.1278596] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Sadanandan Rajapriya
- Department of BiochemistryBharathi Women’s College (Affiliated to University of Madras), Chennai, Tamil Nadu, India
| | - Arumugam Geetha
- Department of BiochemistryBharathi Women’s College (Affiliated to University of Madras), Chennai, Tamil Nadu, India
| | - Kavasseri Ganesan Kripa
- Department of Biochemistry, School of Life Sciences, Vels University, Chennai, Tamil Nadu, India
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Bettaieb A, Chahed S, Bachaalany S, Griffey S, Hammock BD, Haj FG. Soluble Epoxide Hydrolase Pharmacological Inhibition Ameliorates Experimental Acute Pancreatitis in Mice. Mol Pharmacol 2015; 88:281-90. [PMID: 25993999 PMCID: PMC4518092 DOI: 10.1124/mol.114.097501] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Accepted: 05/20/2015] [Indexed: 01/15/2023] Open
Abstract
Acute pancreatitis (AP) is an inflammatory disease, and is one of the most common gastrointestinal disorders worldwide. Soluble epoxide hydrolase (sEH; encoded by Ephx2) deficiency and pharmacological inhibition have beneficial effects in inflammatory diseases. Ephx2 whole-body deficiency mitigates experimental AP in mice, but the suitability of sEH pharmacological inhibition for treating AP remains to be determined. We investigated the effects of sEH pharmacological inhibition on cerulein- and arginine-induced AP using the selective sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), which was administered before and after induction of pancreatitis. Serum amylase and lipase levels were lower in TPPU-treated mice compared with controls. In addition, circulating levels and pancreatic mRNA of the inflammatory cytokines tumor necrosis factor-α, interleukin Il-1β, and Il-6 were reduced in TPPU-treated mice. Moreover, sEH pharmacological inhibition before and after induction of pancreatitis was associated with decreased cerulein- and arginine-induced nuclear factor-κB inflammatory response, endoplasmic reticulum stress, and cell death. sEH pharmacological inhibition before and after induction of pancreatitis mitigated cerulein- and arginine-induced AP. This work suggests that sEH pharmacological inhibition may be of therapeutic value in acute pancreatitis.
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Affiliation(s)
- Ahmed Bettaieb
- Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
| | - Samah Chahed
- Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
| | - Santana Bachaalany
- Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
| | - Stephen Griffey
- Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
| | - Bruce D Hammock
- Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
| | - Fawaz G Haj
- Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
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Abstract
SIGNIFICANCE Cystic fibrosis (CF) is the most common lethal genetic disorder in the Caucasian people. It is due to the mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene located on the long arm of the chromosome 7, which encodes for CFTR protein. The latter, an adenosine triphosphate binding cassette, is a transmembrane chloride channel that is also involved in glutathione transport. As glutathione/glutathione disulfide constitutes the most important pool of cellular redox systems, CFTR defects could thus disrupt the intracellular redox balance. Resulting multisystemic diseases are essentially characterized by a chronic respiratory failure, a pancreatic insufficiency, an essential fatty acid deficiency (EFAD), and inadequate levels of antioxidant vitamins. RECENT ADVANCES The pathophysiology of CF is complex; however, several mechanisms are proposed, including oxidative stress (OxS) whose implication is recognized and has been clearly demonstrated in CF airways. CRITICAL ISSUES Little is known about OxS intrinsic triggers and its own involvement in intestinal lipid disorders. Despite the regular administration of pancreatic supplements, high-fat high-calorie diets, and antioxidant fat-soluble vitamins, there is a persistence of steatorrhea, EFAD, and harmful OxS. Intriguingly, several trials with elevated doses of antioxidant vitamins have not yielded significant improvements. FUTURE DIRECTIONS The main sources and self-maintenance of OxS in CF should be clarified to improve treatment of patients. Therefore, this review will discuss the potential sources and study the mechanisms of OxS in the intestine, known to develop various complications, and its involvement in intestinal lipid disorders in CF patients.
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Affiliation(s)
- Marie-Laure Kleme
- 1 Research Centre, CHU Ste-Justine, Université de Montréal , Montréal, Quebec, Canada
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Chvanov M, Huang W, Jin T, Wen L, Armstrong J, Elliot V, Alston B, Burdyga A, Criddle DN, Sutton R, Tepikin AV. Novel lipophilic probe for detecting near-membrane reactive oxygen species responses and its application for studies of pancreatic acinar cells: effects of pyocyanin and L-ornithine. Antioxid Redox Signal 2015; 22:451-64. [PMID: 24635199 PMCID: PMC4323130 DOI: 10.1089/ars.2013.5589] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIMS The aim of this study was to develop a fluorescent reactive oxygen species (ROS) probe, which is preferentially localized in cellular membranes and displays a strong change in fluorescence upon oxidation. We also aimed to test the performance of this probe for detecting pathophysiologically relevant ROS responses in isolated cells. RESULTS We introduced a novel lipophilic ROS probe dihydrorhodamine B octadecyl ester (H2RB-C18). We then applied the new probe to characterize the ROS changes triggered by inducers of acute pancreatitis in pancreatic acinar cells. We resolved ROS changes produced by L-ornithine, L-arginine, cholecystokinin-8, acetylcholine, taurolithocholic acid 3-sulfate, palmitoleic acid ethyl ester, and the bacterial toxin pyocyanin. Particularly prominent ROS responses were induced by pyocyanin and L-ornithine. These ROS responses were accompanied by changes in cytosolic Ca(2+)concentration ([Ca(2+)]i), mitochondrial membrane potential (ΔΨ), and NAD(P)H concentration. INNOVATION The study describes a novel sensitive lipophilic ROS probe. The probe is particularly suitable for detecting ROS in near-membrane regions and therefore for reporting the ROS environment of plasma membrane channels and pumps. CONCLUSIONS In our experimental conditions, the novel probe was more sensitive than 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein (CM-H2DCF) and dihydrorhodamine123 (H2R123) and allowed us to resolve ROS responses to secretagogues, pyocyanin, and L-ornithine. Changes in the fluorescence of the new probe were particularly prominent in the peripheral plasma membrane-associated regions. Our findings suggest that the new probe will be a useful tool in studies of the contribution of ROS to the pathophysiology of exocrine pancreas and other organs/tissues.
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Affiliation(s)
- Michael Chvanov
- 1 Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool , Liverpool, United Kingdom
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Wu G, Jiang Q, Zhao CJ, Tong C. Changes in plasma ET-1 and NO in patients with severe acute pancreatitis and effect of alprostadil on ET-1 and NO. Shijie Huaren Xiaohua Zazhi 2015; 23:142-146. [DOI: 10.11569/wcjd.v23.i1.142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To detect the changes in plasma endothelin-1 (ET-1) and nitric oxide (NO) in patients with severe acute pancreatitis and to observe the effect of alprostadil on ET-1 and NO levels.
METHODS: Sixty patients with SAP were randomly divided into two groups: a control group (n = 30) or a combination group (n = 30). The control group received intravenous infusion of somatostatin on the basis of conventional therapy, and the combination group received intravenous infusion of alprostadil and somatostatin on the basis of conventional therapy. Plasma levels of ET-1 and NO were measured at admission, 12 h, 48 h, 72 h, and 1 week after onset, and ET-1/NO ratio was calculated.
RESULTS: Plasma levels of ET-1 and NO initially increased, peaked at 12 h, were still maintained at high levels at 72 h, and then declined at 1 week below the levels at admission. The trend of changes of ET-1 and NO were similar between the two groups from admission to 24 h (ET-1 at admission: 97.7 ng/L ± 14.9 ng/L vs 98.8 ng/L ± 15.6 ng/L; 12 h: 157.4 ng/L ± 14.4 ng/L vs 160.3 ng/L ± 15.8 ng/L; 24 h: 146.0 ng/L ± 18.8 ng/L vs 146.4 ng/L ± 19.2 ng/L; NO at admission: 29.0 µmol/L ± 4.4 µmol/L vs 29.7 µmol/L ± 6.0 µmol/L; 12 h: 40.2 µmol/L ± 3.9 µmol/L vs 41.2 µmol/L ± 5.5 µmol/L; 24 h: 39.7 µmol/L ± 4.7 µmol/L vs 39.7 µmol/L ± 4.6 µmol/L; P > 0.05 for all). The levels of ET-1 decreased more significantly from 48 h to 1 week in the combination group (48 h: 134.1 ng/L ± 18.5 ng/L vs 128.3 ng/L ± 17.8 ng/L; 72 h: 99.5 ng/L ± 16.6 ng/L vs 109.8 ng/L ± 17.3 ng/L; 1 wk: 71.4 ng/L ± 12.1 ng/L vs 78.8 ng/L ± 13.3 ng/L; P < 0.05 for all), while the levels of NO decreased more significantly in the control group (48 h: 30.1 µmol/L ± 4.9 µmol/L vs 33.8 µmol/L ± 4.1 µmol/L; 72 h: 22.2 µmol/L ± 4.8 µmol/L vs 28.0 µmol/L ± 4.2 µmol/L; 1 wk: 17.0 µmol/L ± 3.7 µmol/L vs 20.2 µmol/L ± 3.4 µmol/L; P < 0.05 for all).
CONCLUSION: ET-1 and NO are important factors mediating microcirculation disturbance in SAP. Alprostadil can ameliorate pancreatic microcirculation possibly by altering ET-1 and NO expression.
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Wang YH. Therapeutic effect of α-lipoic acid against acute pancreatitis in rats. Shijie Huaren Xiaohua Zazhi 2014; 22:2887-2892. [DOI: 10.11569/wcjd.v22.i20.2887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the protective effects of α-lipoic acid (ALA) against acute pancreatitis (AP) in rats and the underlying mechanism.
METHODS: A rat AP model was induced by injecting 3.5% sodium taurocholate solution into the pancreato-biliary duct. Wistar rats were randomly divided into four groups: a sham-operation (SO) group, an AP group, an AP-normal saline (AP-NS) group and an AP-ALA group (intraperitoneal injection of ALA, 1 mg/kg). The levels of serum amylase, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), pancreatic superoxide dismutase (SOD), malondialdehyde (MDA), and the expression of cyclooxygenase 2 (COX-2) were measured at 1, 3, 6, 9 and 12 h after operation. Pancreatic histological changes were observed.
RESULTS: In the AP and AP-NS groups, the levels of serum amylase, TNF-α, ICAM-1, pancreatic SOD, and the expression of COX-2 were significantly increased, and pancreatic MDA level was decreased compared with the SO group. Optical microscopy revealed pancreatic edema, adhesion, necrosis, and bloody ascites at different time points in the SO AP and AP-NS groups. ALA could decrease the levels of serum amylase and pancreatic MDA, improve the pathological changes in the pancreas and inhibit the release of serum TNF-α, ICAM-1 and COX-2.
CONCLUSION: α-lipoic acid as an antioxidant plays a protective role in AP by restraining the production of TNF-α, ICAM-1 and COX-2.
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Abstract
PURPOSE OF REVIEW Enteral nutrition has emerged as one of the most effective treatments in the early management of patients with acute pancreatitis. The original rationale for nutrition in acute pancreatitis, dating back to the mid-20th century, was to provide full nutritional requirements but avoid stimulating exocrine pancreatic secretion. The purpose of this article is to review the recent clinical studies of enteral nutrition in acute pancreatitis to revise the rationale and develop a contemporary conceptual framework for nutritional management of this disease. RECENT FINDINGS Several recent randomized controlled trials dispel the outdated concept of 'pancreatic rest', which equates with gut neglect, and offer 'gut rousing' as a preferred concept. The new concept postulates that gastrointestinal (dys)function has a discernible impact on the outcomes of patients with acute pancreatitis. Further, timely administration of appropriate intraluminal modalities prevents or mitigates the gastrointestinal dysfunction. SUMMARY Nutritional management in acute pancreatitis should aim primarily at maintaining the gastrointestinal function. Providing full nutritional requirements and avoiding pancreatic exocrine stimulation should be considered as secondary aims.
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Affiliation(s)
- Maxim S Petrov
- Department of Surgery, The University of Auckland, Auckland, New Zealand.
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Yang LJ, Wan R, Shen JQ, Shen J, Wang XP. Effect of L-cysteine on remote organ injury in rats with severe acute pancreatitis induced by bile-pancreatic duct obstruction. Hepatobiliary Pancreat Dis Int 2013; 12:428-35. [PMID: 23924502 DOI: 10.1016/s1499-3872(13)60067-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Remote organ failure occurs in cases of acute pancreatitis (AP); however, the reports on AP induced by pancreatic duct obstruction are rare. In this study we determined the effect of L-cysteine on pancreaticobiliary inflammation and remote organ damage in rats after pancreaticobiliary duct ligation (PBDL). METHODS AP was induced by PBDL in rats with 5/0 silk. Sixty rats were randomly divided into 4 groups. Groups A and B were sham-operated groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). Groups C and D were PBDL groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). The tissue samples of the pancreas and remote organs such as the lung, liver, intestine and kidney were subsequently examined for pathological changes under a light microscope. The samples were also stored for the determination of malondialdehyde and glutathione levels. Blood urea nitrogen (BUN), plasma amylase, ALT and AST levels were determined spectrophotometrically using an automated analyzer. Also, we evaluated the effect of L-cysteine on remote organ injury in rats with AP induced by retrograde infusion of 3.5% sodium taurocholate (NaTc) into the bile-pancreatic duct. RESULTS Varying degrees of injury in the pancreas, lung, liver, intestine and kidney were observed in the rats 24 hours after PBDL. The severity of injury to the lung, liver and intestine was attenuated, while injury status was not changed significantly in the pancreas and kidney after L-cysteine treatment. Oxidative stress was also affected by L-cysteine in PBDL-treated rats. The concentration of tissue malondialdehyde decreased in the pancreas and remote organs of PBDL and L-cysteine administrated rats, and the concentration of glutathione increased more significantly than that of the model control group. However, L-cysteine administration reduced the severity of injury in remote organs but not in the pancreas in rats with NaTc-induced AP. CONCLUSION L-cysteine treatment attenuated multiple organ damage at an early stage of AP in rats and modulated the oxidant/antioxidant imbalance.
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Affiliation(s)
- Li-Juan Yang
- Department of Gastroenterology, and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China
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Akyazi I, Eraslan E, Gülçubuk A, Ekiz EE, Çırakli ZL, Haktanir D, Bala DA, Özkurt M, Matur E, Özcan M. Long-term aspirin pretreatment in the prevention of cerulein-induced acute pancreatitis in rats. World J Gastroenterol 2013; 19:2894-2903. [PMID: 23704822 PMCID: PMC3660814 DOI: 10.3748/wjg.v19.i19.2894] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2012] [Revised: 01/15/2013] [Accepted: 02/06/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of long term pretreatment with low-, medium- and high-dose aspirin (acetylsalicylic acid, ASA) on a model of acute pancreatitis (AP) induced in rats.
METHODS: Forty male Wistar rats were used. Three experimental groups, each consisting of eight animals, received low- (5 mg/kg per day), medium- (150 mg/kg per day) and high-dose (350 mg/kg per day) ASA in supplemented pellet chow for 100 d. Eight animals, serving as the AP-control group, and another eight, serving as reference value (RV) group, were fed with standard pellet chow for the same period. After pretreatment, AP was induced in the experimental animals by intraperitoneal administration of cerulein (2 × 50 μg/kg), while the RV group received saline in the same way. Twelve hours after the second injection, the animals were sacrificed. Pancreatic tissue and plasma samples were collected. One part of the collected pancreatic tissues was used for histopathological evaluation, and the remaining portion was homogenized. Cytokine levels [tumor necrosis factor, interleukin (IL)-1β, IL-6], hemogram parameters, biochemical parameters (amylase and lipase), nuclear factor-κB, aspirin triggered lipoxins and parameters related to the antioxidant system (malondialdehyde, nitric oxide, hemeoxygenase-1, catalase and superoxide dismutase) were measured.
RESULTS: Cerulein administration induced mild pancreatitis, characterized by interstitial edema (total histopathological score of 5.88 ± 0.44 vs 0.25 ± 0.16, P < 0.001). Subsequent pancreatic tissue damage resulted in an increase in amylase (2829.71 ± 772.48 vs 984.57 ± 49.22 U/L, P = 0.001) and lipase (110.14 ± 75.84 U/L vs 4.71 ± 0.78 U/L, P < 0.001) in plasma, and leucocytes (6.89 ± 0.48 vs 4.36 ± 0.23, P = 0.001) in peripheral blood. Cytokines, IL-1β (18.81 ± 2.55 pg/μg vs 6.65 ± 0.24 pg/μg, P = 0.002) and IL-6 (14.62 ± 1.98 pg/μg vs 9.09 ± 1.36 pg/μg, P = 0.04) in pancreatic tissue also increased. Aspirin pretreatment reduced the increase in the aforementioned parameters to a certain degree and partially improved the histopathological alterations caused by cerulein. No evidence of side effects related to chronic ASA administration (e.g., inflammation or bleeding) was observed in the gastrointestinal tract in macroscopic and histopathological examination.
CONCLUSION: Long term ASA pretreatment could prevent and/or ameliorate certain hematological, serological and histological alterations caused by cerulein-induced AP.
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Abstract
OBJECTIVES Oxidative stress has been implicated in the pathogenesis of chronic pancreatitis (CP) and pancreatic cancer (PC). The study aim was to assess the oxidative stress markers and antioxidant defense system in patients with CP and those with PC. METHODS Activities of superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1) and concentrations of reduced glutathione, conjugated dienes in low-density lipoprotein (CD/LDL) and oxidized LDL (ox-LDL/LDL) were assessed in 50 PC and 50 CP patients and 50 age and sex-matched controls. RESULTS Comparison of PC and CP groups to controls found the following changes: glutathione peroxidase 1 (GPX1) (-20.2%, -25.5%; P < 0.001), glutathione reductase (GR) (-9.5%, -11.9%; P < 0.05), SOD1 (+22.9%; P < 0.01), CAT (-10.6%; P < 0.05), PON1-A (-34.3%, -16.0%; P < 0.001), PON1-L (-44.2%; -17.0%; P < 0.01), conjugated dienes in LDL (CD/LDL) (+20%, +33.3%; P < 0.05) and ox-LDL/LDL (+42.2%, +14.4%; P < 0.05). The patients with PC had changed activities and levels of SOD1 (+24.2%), CAT (-10.4); P < 0.01), PON1-A (-21.7%), PON1-L (-32.9%), and ox-LDL/LDL (+24.3%); (all P < 0.01) compared with the patients with CP. CONCLUSIONS Reduced antioxidant defense system capacity and increased markers of oxidative stress were found in PC and CP. PON1-L and CAT activities, along with ox-LDL/LDL levels, were the independent factors differentiating the patients with PC from the patients with CP.
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Seyhun E, Malo A, Schäfer C, Moskaluk CA, Hoffmann RT, Göke B, Kubisch CH. Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, acinar cell damage, and systemic inflammation in acute pancreatitis. Am J Physiol Gastrointest Liver Physiol 2011; 301:G773-82. [PMID: 21778463 DOI: 10.1152/ajpgi.00483.2010] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In acute pancreatitis, endoplasmic reticulum (ER) stress prompts an accumulation of malfolded proteins inside the ER, initiating the unfolded protein response (UPR). Because the ER chaperone tauroursodeoxycholic acid (TUDCA) is known to inhibit the UPR in vitro, this study examined the in vivo effects of TUDCA in an acute experimental pancreatitis model. Acute pancreatitis was induced in Wistar rats using caerulein, with or without prior TUDCA treatment. UPR components were analyzed, including chaperone binding protein (BiP), phosphorylated protein kinase-like ER kinase (pPERK), X-box binding protein (XBP)-1, phosphorylated c-Jun NH(2)-terminal kinase (pJNK), CCAAT/enhancer binding protein homologues protein, and caspase 12 and 3 activation. In addition, pancreatitis biomarkers were measured, such as serum amylase, trypsin activation, edema formation, histology, and the inflammatory reaction in pancreatic and lung tissue. TUDCA treatment reduced intracellular trypsin activation, edema formation, and cell damage, while leaving amylase levels unaltered. The activation of myeloperoxidase was clearly reduced in pancreas and lung. Furthermore, TUDCA prevented caerulein-induced BiP upregulation, reduced XBP-1 splicing, and caspase 12 and 3 activation. It accelerated the downregulation of pJNK. In controls without pancreatitis, TUDCA showed cytoprotective effects including pPERK signaling and activation of downstream targets. We concluded that ER stress responses activated in acute pancreatitis are grossly attenuated by TUDCA. The chaperone reduced the UPR and inhibited ER stress-associated proapoptotic pathways. TUDCA has a cytoprotective potential in the exocrine pancreas. These data hint at new perspectives for an employment of chemical chaperones, such as TUDCA, in prevention of acute pancreatitis.
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Affiliation(s)
- Ersin Seyhun
- Department of Internal Medicine II, Campus Grobhadern, University of Munich, Germany
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Fujimori N, Oono T, Igarashi H, Ito T, Nakamura T, Uchida M, Coy DH, Jensen RT, Takayanagi R. Vasoactive intestinal peptide reduces oxidative stress in pancreatic acinar cells through the inhibition of NADPH oxidase. Peptides 2011; 32:2067-2076. [PMID: 21924308 DOI: 10.1016/j.peptides.2011.08.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2011] [Revised: 08/31/2011] [Accepted: 08/31/2011] [Indexed: 12/16/2022]
Abstract
Vasoactive intestinal peptide (VIP) attenuates experimental acute pancreatitis (AP) by inhibition of cytokine production from inflammatory cells. It has been suggested that reactive oxygen species (ROS) as well as cytokines play pivotal roles in the early pathophysiology of AP. This study aimed to clarify the effect of VIP on the oxidative condition in pancreas, especially pancreatic acinar cells (acini). Hydrogen peroxide (H(2)O(2))-induced intracellular ROS, assessed with CM-H(2)DCFDA, increased time- and dose-dependently in acini isolated from rats. Cell viability due to ROS-induced cellular damage, evaluated by MTS assay, was decreased with ≥100 μmol/L H(2)O(2). VIP significantly inhibited ROS production from acini and increased cell viability in a dose-dependent manner. Expression of antioxidants including catalase, glutathione reductase, superoxide dismutase (SOD) 1 and glutathione peroxidase was not altered by VIP except for SOD2. Furthermore, Nox1 and Nox2, major components of NADPH oxidase, were expressed in pancreatic acini, and significantly increased after H(2)O(2) treatment. Also, NADPH oxidase activity was provoked by H(2)O(2). VIP decreased NADPH oxidase activity, which was abolished by PKA inhibitor H89. These results suggested that VIP affected the mechanism of ROS production including NADPH oxidase through induction of a cAMP/PKA pathway. In conclusion, VIP reduces oxidative stress in acini through the inhibition of NADPH oxidase. These results combined with findings of our previous study suggest that VIP exerts its protective effect in pancreatic damage, not only through an inhibition of cytokine production, but also through a reduction of the injury caused by oxidative stress.
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Affiliation(s)
- Nao Fujimori
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
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Ozkan E, Akyüz C, Dulundu E, Topaloğlu U, Sehirli AÖ, Ercan F, Sener G. Protective effects of lycopene on cerulein-induced experimental acute pancreatitis in rats. J Surg Res 2011; 176:232-8. [PMID: 22079843 DOI: 10.1016/j.jss.2011.09.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2011] [Revised: 08/25/2011] [Accepted: 09/02/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND The purpose of our study was to evaluate the protective effect of the strong antioxidant and anti-inflammatory agent, lycopene, on oxidative stress in a rat model of cerulein-induced acute edematous pancreatitis. METHODS Sprague-Dawley rats were pretreated with lycopene (50 mg/kg, i.p.) or saline 15 min before cerulein was given 20 μg/kg (i.p.) at 1-h intervals within 4 h. Twelve hours after cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and proinflammatory cytokines (TNF-α and IL-1ß). Pancreatic tissues were taken for the determination of tissue glutathione (GSH) and malondialdehyde (MDA) levels, Na(+)/K(+)-ATPase, and myeloperoxidase (MPO) activities. Tissue samples were also examined histologically. RESULTS Acute pancreatitis caused significant decrease in tissue GSH levels and Na(+)/K(+)-ATPase activity, while pancreatic MDA levels and MPO activity were increased. Furthermore, TNF-α, IL-1ß, and amylase lipase levels were also significantly increased. On the other hand, lycopene pretreatment reserved all these biochemical indices as well as histopathologic alterations that were induced by cerulein. CONCLUSIONS According to the results, lycopene protects the pancreatic tissues from oxidative damage induced by cerulein, and this effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation. These results suggest that high dietary intake of tomatoes may have protective effects against acute pancreatitis.
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Affiliation(s)
- Erkan Ozkan
- Department of 5th Surgery, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey
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Petrov MS, Chong V, Windsor JA. Infected pancreatic necrosis: Not necessarily a late event in acute pancreatitis. World J Gastroenterol 2011; 17:3173-6. [PMID: 21912463 PMCID: PMC3158390 DOI: 10.3748/wjg.v17.i27.3173] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2010] [Revised: 01/24/2011] [Accepted: 01/31/2011] [Indexed: 02/06/2023] Open
Abstract
It is widely believed that infection of pancreatic necrosis is a late event in the natural course of acute pancreatitis. This paper discusses the available data on the timing of pancreatic infection. It appears that infected pancreatic necrosis occurs early in almost a quarter of patients. This has practical implications for the type, timing and duration of preventive strategies used in these patients. There are also implications for the classification of severity in patients with acute pancreatitis. Given that the main determinants of severity are both local and systemic complications and that they can occur both early and late in the course of acute pancreatitis, the classification of severity should be based on their presence or absence rather than on when they occur. To do otherwise, and in particular overlook early infected pancreatic necrosis, may lead to a misclassification error and fallacies of clinical studies in patients with acute pancreatitis.
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