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Sastre J, Pérez S, Sabater L, Rius-Pérez S. Redox signaling in the pancreas in health and disease. Physiol Rev 2025; 105:593-650. [PMID: 39324871 DOI: 10.1152/physrev.00044.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 09/11/2024] [Accepted: 09/17/2024] [Indexed: 09/27/2024] Open
Abstract
This review addresses oxidative stress and redox signaling in the pancreas under healthy physiological conditions as well as in acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. Physiological redox homeodynamics is maintained mainly by NRF2/KEAP1, NF-κB, protein tyrosine phosphatases, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), and normal autophagy. Depletion of reduced glutathione (GSH) in the pancreas is a hallmark of acute pancreatitis and is initially accompanied by disulfide stress, which is characterized by protein cysteinylation without increased glutathione oxidation. A cross talk between oxidative stress, MAPKs, and NF-κB amplifies the inflammatory cascade, with PP2A and PGC1α as key redox regulatory nodes. In acute pancreatitis, nitration of cystathionine-β synthase causes blockade of the transsulfuration pathway leading to increased homocysteine levels, whereas p53 triggers necroptosis in the pancreas through downregulation of sulfiredoxin, PGC1α, and peroxiredoxin 3. Chronic pancreatitis exhibits oxidative distress mediated by NADPH oxidase 1 and/or CYP2E1, which promotes cell death, fibrosis, and inflammation. Oxidative stress cooperates with mutant KRAS to initiate and promote pancreatic adenocarcinoma. Mutant KRAS increases mitochondrial reactive oxygen species (ROS), which trigger acinar-to-ductal metaplasia and progression to pancreatic intraepithelial neoplasia (PanIN). ROS are maintained at a sufficient level to promote cell proliferation, while avoiding cell death or senescence through formation of NADPH and GSH and activation of NRF2, HIF-1/2α, and CREB. Redox signaling also plays a fundamental role in differentiation, proliferation, and insulin secretion of β-cells. However, ROS overproduction promotes β-cell dysfunction and apoptosis in type 1 and type 2 diabetes.
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Affiliation(s)
- Juan Sastre
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
| | - Salvador Pérez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
| | - Luis Sabater
- Liver, Biliary and Pancreatic Unit, Hospital Clínico, Department of Surgery, Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Sergio Rius-Pérez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
- Department of Cell Biology, Functional Biology and Physical Anthropology, Faculty of Biology, University of Valencia, Valencia, Spain
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Poulsen VV, Hadi A, Werge MP, Karstensen JG, Novovic S. Circulating Biomarkers Involved in the Development of and Progression to Chronic Pancreatitis-A Literature Review. Biomolecules 2024; 14:239. [PMID: 38397476 PMCID: PMC10887223 DOI: 10.3390/biom14020239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 02/13/2024] [Accepted: 02/16/2024] [Indexed: 02/25/2024] Open
Abstract
Chronic pancreatitis (CP) is the end-stage of continuous inflammation and fibrosis in the pancreas evolving from acute- to recurrent acute-, early, and, finally, end-stage CP. Currently, prevention is the only way to reduce disease burden. In this setting, early detection is of great importance. Due to the anatomy and risks associated with direct sampling from pancreatic tissue, most of our information on the human pancreas arises from circulating biomarkers thought to be involved in pancreatic pathophysiology or injury. The present review provides the status of circulating biomarkers involved in the development of and progression to CP.
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Affiliation(s)
- Valborg Vang Poulsen
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
| | - Amer Hadi
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
| | - Mikkel Parsberg Werge
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
| | - John Gásdal Karstensen
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
- Department of Clinical Medicine, University of Copenhagen, 2000 Copenhagen, Denmark
| | - Srdan Novovic
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
- Department of Clinical Medicine, University of Copenhagen, 2000 Copenhagen, Denmark
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Silva-Vaz P, Jarak I, Rato L, Oliveira PF, Morgado-Nunes S, Paulino A, Castelo-Branco M, Botelho MF, Tralhão JG, Alves MG, Abrantes AM. Plasmatic Oxidative and Metabonomic Profile of Patients with Different Degrees of Biliary Acute Pancreatitis Severity. Antioxidants (Basel) 2021; 10:antiox10060988. [PMID: 34205667 PMCID: PMC8234183 DOI: 10.3390/antiox10060988] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 06/11/2021] [Accepted: 06/15/2021] [Indexed: 01/06/2023] Open
Abstract
Acute pancreatitis (AP) is an inflammatory process of the pancreas with variable involvement of the pancreatic and peripancreatic tissues and remote organ systems. The main goal of this study was to evaluate the inflammatory biomarkers, oxidative stress (OS), and plasma metabolome of patients with different degrees of biliary AP severity to improve its prognosis. Twenty-nine patients with biliary AP and 11 healthy controls were enrolled in this study. We analyzed several inflammatory biomarkers, multifactorial scores, reactive oxygen species (ROS), antioxidants defenses, and the plasma metabolome of biliary AP and healthy controls. Hepcidin (1.00), CRP (0.94), and SIRI (0.87) were the most accurate serological biomarkers of AP severity. OS played a pivotal role in the initial phase of AP, with significant changes in ROS and antioxidant defenses relating to AP severity. Phenylalanine (p < 0.05), threonine (p < 0.05), and lipids (p < 0.01) showed significant changes in AP severity. The role of hepcidin and SIRI were confirmed as new prognostic biomarkers of biliary AP. OS appears to have a role in the onset and progression of the AP process. Overall, this study identified several metabolites that may predict the onset and progression of biliary AP severity, constituting the first metabonomic study in the field of biliary AP.
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Affiliation(s)
- Pedro Silva-Vaz
- Health Sciences Research Centre, University of Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal;
- General Surgery Department, Hospital Amato Lusitano, Unidade Local de Saúde de Castelo Branco, 6000-085 Castelo Branco, Portugal;
- Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal
- Clinical Academic Centre of Beiras (CACB), 6200-506 Covilhã, Portugal;
- Correspondence: ; Tel.: +351-966-498-337
| | - Ivana Jarak
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal;
| | - Luís Rato
- Health School of the Polytechnic of Guarda, 6300-559 Guarda, Portugal;
| | - Pedro F. Oliveira
- QOPNA & LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal;
| | - Sara Morgado-Nunes
- Clinical Academic Centre of Beiras (CACB), 6200-506 Covilhã, Portugal;
- Polytechnic Institute of Castelo Branco, Escola Superior de Gestão, 6000-084 Castelo Branco, Portugal
| | - Aida Paulino
- General Surgery Department, Hospital Amato Lusitano, Unidade Local de Saúde de Castelo Branco, 6000-085 Castelo Branco, Portugal;
- Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal
- Clinical Academic Centre of Beiras (CACB), 6200-506 Covilhã, Portugal;
| | - Miguel Castelo-Branco
- Health Sciences Research Centre, University of Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal;
- Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal
- Clinical Academic Centre of Beiras (CACB), 6200-506 Covilhã, Portugal;
| | - Maria Filomena Botelho
- Biophysics Institute, Faculty of Medicina, University of Coimbra, 3000-548 Coimbra, Portugal; (M.F.B.); (J.G.T.); (A.M.A.)
- Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicina, University of Coimbra, 3000-548 Coimbra, Portugal
- CNC.IBILI Consortium/Center for Innovation Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), 3000-561 Coimbra, Portugal
| | - José Guilherme Tralhão
- Biophysics Institute, Faculty of Medicina, University of Coimbra, 3000-548 Coimbra, Portugal; (M.F.B.); (J.G.T.); (A.M.A.)
- Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicina, University of Coimbra, 3000-548 Coimbra, Portugal
- CNC.IBILI Consortium/Center for Innovation Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), 3000-561 Coimbra, Portugal
- Surgery Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Faculty of Medicina, University Hospital, 3000-075 Coimbra, Portugal
| | - Marco G. Alves
- Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal;
| | - Ana Margarida Abrantes
- Biophysics Institute, Faculty of Medicina, University of Coimbra, 3000-548 Coimbra, Portugal; (M.F.B.); (J.G.T.); (A.M.A.)
- Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicina, University of Coimbra, 3000-548 Coimbra, Portugal
- CNC.IBILI Consortium/Center for Innovation Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), 3000-561 Coimbra, Portugal
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Thromboxane A2 receptor contributes to the activation of rat pancreatic stellate cells induced by 8-epi-prostaglandin F2α. Chin Med J (Engl) 2020; 133:1429-1435. [PMID: 32501828 PMCID: PMC7339349 DOI: 10.1097/cm9.0000000000000838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α). METHODS TxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10, 10, 10 mol/L) for 48 h, and SQ29548 (10, 10, and 10 mol/L), a TxA2r-specific antagonist for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10 mol/L) for 2 h, followed by 10 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student's t test. RESULTS TxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2α significantly increased mRNA levels of α-SMA (10 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t = 10.70, P < 0.001; 10 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t = 10.83, P < 0.001; 10 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t = 11.40, P < 0.001) and collagen I (10 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t = 15.41, P < 0.001) and α-SMA (10 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t = 15.17, P < 0.001; 10 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t = 11.29, P < 0.001; 10 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t = 12.86, P < 0.001). After being treated with SQ29548 (10 mol/L) and then 8-epi-PGF2α (10 mol/L), the mRNA levels of α-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t = 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group. CONCLUSIONS The results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.
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Antioxidants for Pancreatic Functions in Chronic Pancreatitis: A Double-blind Randomized Placebo-controlled Pilot Study. J Clin Gastroenterol 2020; 54:284-293. [PMID: 30789855 DOI: 10.1097/mcg.0000000000001178] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Antioxidants (AO) supplementation in chronic pancreatitis (CP) has been evaluated for pain. But it is not clear whether AO in CP have an effect on pancreatic functions and other clinical outcomes. We evaluated effect of AO on endocrine function in CP. MATERIALS AND METHODS Double-blind placebo (PL)-controlled randomized pilot study on 107 patients with CP assigned to receive daily combined AO or PL for 6 months. Primary outcome was: improvement in endocrine function (Homeostasis Model Assessment-Insulin Resistance). Secondary outcome measures were: improvement in C-peptide, Qualitative Insulin Sensitivity Check Index, exocrine pancreatic function (fecal elastase), surrogate markers of fibrosis (platelet-derived growth factor BB, transforming growth factor-β1, α-smooth muscle actin), quality of life (QOL), pain, nutritional status, markers of oxidative stress (OS), AO status, and inflammation. RESULTS There was an increase in levels of serum selenium (107.2±26.9 to 109.7±26.9 vs. 104.1±28.6 to 124.0±33.6 μg/L, P=0.022) and serum vitamin E [0.58 (range, 0.27-3.22) to 0.66 (range, 0.34-1.98) vs. 0.63 (range, 0.28-1.73) to 1.09 (range, 0.25-2.91) mg/dL, P=0.001] in the AO than the PL group. However, no significant differences were observed between groups in any of the primary or secondary outcome measures. CONCLUSIONS Supplementation with AO to patients with CP causes a sustained increase in blood levels of AO; however, it has no addition benefit over PL on endocrine and exocrine functions, markers of fibrosis, OS and inflammation, nutritional status, pain and QOL. Further larger studies with adequate sample size are required.
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Śliwińska-Mossoń M, Milnerowicz S, Milnerowicz H. Diabetes mellitus secondary to pancreatic diseases (type 3c): The effect of smoking on the exocrine-endocrine interactions of the pancreas. Diab Vasc Dis Res 2018; 15:243-259. [PMID: 29558826 DOI: 10.1177/1479164118764062] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
The present study was conducted to ascertain how cigarette smoke affects the exocrine-endocrine interactions of the human pancreas with diabetes mellitus secondary to pancreatic diseases (type 3c). Blood has been collected from smoking and non-smoking healthy individuals as well as from patients with diagnosed chronic pancreatitis and diabetes type 3c. The concentrations of interleukin-6, endothelin-1 and insulin in the plasma were determined by enzyme-linked immunosorbent assay (ELISA) tests. The activities of amylase and lipase in the serum, as well as the lipid profile, creatinine, uric acid and urea concentrations, were measured using colorimetric methods. Samples of normal pancreatic tissue and chronic pancreatitis were verified histopathologically and then interleukin-6, endothelin-1, insulin and glucagon were localized by immunohistochemical staining using a monoclonal anti-human antibody. The highest levels of interleukin-6 and endothelin-1 and the lowest levels of insulin and glucagon intensity from the immunostaining were observed in smoking patients with diabetes. In all smoking patients with pancreatitis and diabetes, there was a significant elevation in interleukin-6 and endothelin-1 concentration and amylase and lipase activities, hyperlipidaemia and a lower value of estimated glomerular filtration rate and blood urea nitrogen when compared to non-smokers. Our study confirmed that smoking exerts a pro-inflammatory effect and disturbs the exocrine-endocrine interactions of the pancreas.
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Affiliation(s)
- Mariola Śliwińska-Mossoń
- 1 Department of Biomedical and Environmental Analyses, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wrocław Medical University, Wrocław, Poland
| | - Stanisław Milnerowicz
- 2 Department and Clinic of Gastrointestinal and General Surgery, Faculty of Postgraduate Medical Training, Wrocław Medical University, Wrocław, Poland
| | - Halina Milnerowicz
- 1 Department of Biomedical and Environmental Analyses, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wrocław Medical University, Wrocław, Poland
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Subramanian VS, Srinivasan P, Said HM. Uptake of ascorbic acid by pancreatic acinar cells is negatively impacted by chronic alcohol exposure. Am J Physiol Cell Physiol 2016; 311:C129-35. [PMID: 27122159 DOI: 10.1152/ajpcell.00042.2016] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 04/20/2016] [Indexed: 12/21/2022]
Abstract
Vitamin C (ascorbic acid, AA) is indispensable for normal metabolism of all mammalian cells including pancreatic acinar cells (PACs). PACs obtain AA from their surroundings via transport across the cell membrane. Chronic alcohol exposure negatively affects body AA homeostasis; it also inhibits uptake of other micronutrients into PACs, but its effect on AA uptake is not clear. We examined this issue using both in vitro (266-6 cells) and in vivo (mice) models of chronic alcohol exposure. First, we determined the relative expression of the AA transporters 1 and 2 [i.e., sodium-dependent vitamin C transporter-1 (SVCT-1) and SVCT-2] in mouse and human PACs and found SVCT-2 to be the predominant transporter. Chronic exposure of 266-6 cells to alcohol significantly inhibited AA uptake and caused a marked reduction in SVCT-2 expression at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Similarly, chronic alcohol feeding of mice significantly inhibited AA uptake and caused a marked reduction in level of expression of the SVCT-2 protein, mRNA, and hnRNA. These findings suggest possible involvement of transcriptional mechanism(s) in mediating chronic alcohol effect on AA uptake by PACs. We also observed significant epigenetic changes (histone modifications) in the Slc23a2 gene (reduction in H3K4me3 level and an increase in H3K27me3 level) in the alcohol-exposed 266-6 cells. These findings show that chronic alcohol exposure inhibits PAC AA uptake and that the effect is mediated, in part, at the level of transcription of the Slc23a2 gene and may involve epigenetic mechanism(s).
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Affiliation(s)
- Veedamali S Subramanian
- Department of Medicine, University of California, Irvine, California; Department of Physiology, University of California, Irvine, California; Department of Biophysics, University of California, Irvine, California; Department of Veterans Affairs Medical Center, Long Beach, California
| | - Padmanabhan Srinivasan
- Department of Medicine, University of California, Irvine, California; Department of Physiology, University of California, Irvine, California; Department of Biophysics, University of California, Irvine, California; Department of Veterans Affairs Medical Center, Long Beach, California
| | - Hamid M Said
- Department of Medicine, University of California, Irvine, California; Department of Physiology, University of California, Irvine, California; Department of Biophysics, University of California, Irvine, California; Department of Veterans Affairs Medical Center, Long Beach, California
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Zhang LP, Kline RH, Deevska G, Ma F, Nikolova-Karakashian M, Westlund KN. Alcohol and high fat induced chronic pancreatitis: TRPV4 antagonist reduces hypersensitivity. Neuroscience 2015; 311:166-79. [PMID: 26480812 PMCID: PMC4670827 DOI: 10.1016/j.neuroscience.2015.10.028] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Revised: 09/23/2015] [Accepted: 10/13/2015] [Indexed: 02/07/2023]
Abstract
The pathogenesis of pain in chronic pancreatitis is poorly understood, and its treatment can be a major clinical challenge. Surgical and other invasive methods have variable outcomes that can be unsatisfactory. Therefore, there is a great need for further discovery of the pathogenesis of pancreatitis pain and new therapeutic targets. Human and animal studies indicate a critical role for oxidative stress and activation of transient receptor potential (TRP) cation channel subfamily members TRPV1 and TRPA1 on pancreatic nociceptors in sensitization mechanisms that result in pain. However, the in vivo role of transient receptor potential cation channel subfamily V member 4 (TRPV4) in chronic pancreatitis needs further evaluation. The present study characterized a rat alcohol/high fat diet (AHF)-induced chronic pancreatitis model with hypersensitivity, fibrotic pathology, and fat vacuolization consistent with the clinical syndrome. The rats with AHF-induced pancreatitis develop referred visceral pain-like behaviors, i.e. decreased hindpaw mechanical thresholds and shortened abdominal and hindpaw withdrawal latency to heat. In this study, oxidative stress was characterized as well as the role of TRPV4 in chronic visceral hypersensitivity. Lipid peroxidase and oxidative stress were indicated by increased plasma thiobarbituric acid reactive substances (TBARS) and diminished pancreatic manganese superoxide dismutase (MnSOD). The secondary sensitization associated with AHF-induced pancreatitis was effectively alleviated by the TRPV4 antagonist, HC 067047. Similarity of the results to those with the peripherally restricted μ-opiate receptor agonist, loperamide, suggested TRPV4 channel activated peripheral sensitization. This study using a reliable model that provides pre-clinical correlates of human chronic pancreatitis provides further evidence that TRPV4 channel is a potential therapeutic target for treatment of pancreatitis pain.
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MESH Headings
- Analgesics/pharmacology
- Animals
- Diet, High-Fat
- Disease Models, Animal
- Drug Evaluation, Preclinical
- Ethanol
- Hot Temperature
- Loperamide/pharmacology
- Male
- Morpholines/pharmacology
- Oxidative Stress/drug effects
- Oxidative Stress/physiology
- Pain/drug therapy
- Pain/etiology
- Pain/physiopathology
- Pain Threshold/drug effects
- Pain Threshold/physiology
- Pancreatitis, Chronic/complications
- Pancreatitis, Chronic/drug therapy
- Pancreatitis, Chronic/physiopathology
- Pyrroles/pharmacology
- Random Allocation
- Rats, Inbred F344
- Receptors, Opioid, mu/agonists
- Receptors, Opioid, mu/metabolism
- TRPV Cation Channels/antagonists & inhibitors
- TRPV Cation Channels/metabolism
- Touch
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Affiliation(s)
- L P Zhang
- Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40526-0298, United States
| | - R H Kline
- Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40526-0298, United States
| | - G Deevska
- Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40526-0298, United States
| | - F Ma
- Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40526-0298, United States
| | - M Nikolova-Karakashian
- Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40526-0298, United States
| | - K N Westlund
- Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40526-0298, United States.
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Feng YC, Wang M, Zhu F, Qin RY. Study on acute recent stage pancreatitis. World J Gastroenterol 2014; 20:16138-16145. [PMID: 25473166 PMCID: PMC4239500 DOI: 10.3748/wjg.v20.i43.16138] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2014] [Revised: 05/12/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis (AP) is an inflammatory disease of the pancreas which involves the pancreas and surrounding tissue, and systemic inflammation with a characteristic systemic increase of vascular permeability and increased risk of multiple organ dysfunction. Currently, the pathogenesis of AP is fuzzy, and the diagnosis and treatment need to be standardized. Nevertheless, increased knowledge of AP may achieve more thorough understanding of the pathogenesis. The use of further advanced diagnostic tools and superior treatment, potentially will help clinicians to manage AP at an appropriate stage. However, in view of the multi factorial disease and the complex clinical manifestations, the management of patients with AP is also remaining areas for improvement.
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10
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The antioxidant profiles, lysosomal and membrane enzymes activity in patients with acute pancreatitis. Mediators Inflamm 2014; 2014:376518. [PMID: 25298618 PMCID: PMC4178910 DOI: 10.1155/2014/376518] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2014] [Revised: 08/19/2014] [Accepted: 08/19/2014] [Indexed: 12/20/2022] Open
Abstract
Oxidative stress and inflammatory mediators, such as IL-6, play an important role in the pathophysiology of acute pancreatitis. The study was aimed to assess the degree of the pro/antioxidative imbalance and estimate which antioxidant plays a role in the maintenance of pro/antioxidative balance during acute pancreatitis. The study was investigated in the blood of 32 patients with acute pancreatitis and 37 healthy subjects. IL-6 concentration as early marker of inflammation was determinated. The intensity of oxidative stress was assessed by TBARS concentration. To investigate antioxidative status, the GPx and Cu/Zn SOD activities and the levels of GSH, MT, SH groups, and TRAP were measured. The concentrations of Cu and Zn as ions participating in the maintenance of antioxidant enzymes stability and playing a role in the course of disease were determinated. The activities of GGT, AAP, NAG, and β-GD as markers of tissue damage were also measured. An increase in IL-6 concentration, which correlated with Ranson criteria, and an increase in GPx activity, levels of MT, TBARS, or GGT, and NAG activities in patients group compared to healthy subjects were demonstrated. A decrease in GSH level in patients group compared to control group was noted. The studies suggest that GPx/GSH and MT play the role of the first line of defence against oxidative stress and pro/antioxidant imbalance in the course of acute pancreatitis.
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Camargo E, Santana D, Silva C, Teixeira S, Toyama M, Cotrim C, Landucci E, Antunes E, Muscara M, Costa S. Inhibition of inducible nitric oxide synthase-derived nitric oxide as a therapeutical target for acute pancreatitis induced by secretory phospholipase A2. Eur J Pain 2013; 18:691-700. [DOI: 10.1002/j.1532-2149.2013.00414.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/01/2013] [Indexed: 12/15/2022]
Affiliation(s)
- E.A. Camargo
- Department of Physiology; Federal University of Sergipe; São Cristóvão Brazil
| | - D.G. Santana
- Department of Physiology; Federal University of Sergipe; São Cristóvão Brazil
| | - C.I. Silva
- Department of Pharmacology; Institute of Biomedical Sciences; University of São Paulo (USP); Brazil
| | - S.A. Teixeira
- Department of Pharmacology; Institute of Biomedical Sciences; University of São Paulo (USP); Brazil
| | - M.H. Toyama
- São Vicente Unit; University of São Paulo State (UNESP); São Vicente Brazil
| | - C. Cotrim
- São Vicente Unit; University of São Paulo State (UNESP); São Vicente Brazil
| | - E.C.T. Landucci
- Department of Pharmacology; Faculty of Medical Sciences; State University of Campinas (UNICAMP); São Paulo Brazil
| | - E. Antunes
- Department of Pharmacology; Faculty of Medical Sciences; State University of Campinas (UNICAMP); São Paulo Brazil
| | - M.N. Muscara
- Department of Pharmacology; Institute of Biomedical Sciences; University of São Paulo (USP); Brazil
| | - S.K.P. Costa
- Department of Pharmacology; Institute of Biomedical Sciences; University of São Paulo (USP); Brazil
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Bhardwaj P, Yadav RK. Chronic pancreatitis: role of oxidative stress and antioxidants. Free Radic Res 2013; 47:941-9. [DOI: 10.3109/10715762.2013.804624] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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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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Effect of antioxidant supplementation on surrogate markers of fibrosis in chronic pancreatitis: a randomized, placebo-controlled trial. Pancreas 2013; 42:589-95. [PMID: 23531998 DOI: 10.1097/mpa.0b013e31826dc2d7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES This study aimed to determine the effect of antioxidant (AO) supplementation on surrogate markers of fibrosis in patients with chronic pancreatitis (CP). METHODS In a randomized, placebo (PL)-controlled trial, patients with CP were randomized to groups that were given PL or AO for 3 months. Outcome measures were change in serum levels of transforming growth factor β1 and platelet-derived growth factor AA (PDGF-AA) (primary outcome) as well as blood markers of oxidative stress (thiobarbituric acid-reactive substances) and AO status (ferric-reducing ability of plasma) (secondary outcome). Pain relief and analgesic requirement was also recorded. RESULTS Patients (n = 61; mean [SD] age, 35.2 [10.0]; male patients, 43) were assigned to AO (n = 31) and PL (n = 30) groups. The median (range) percent reduction from baseline to 3 months in levels of PDGF-AA (17.1% [-25.3% to 88.7%] vs 2.8% [-243.1% to 30.2%]; P = 0.001), transforming growth factor β1 (P = 0.573), and thiobarbituric acid-reactive substances (P = 0.207) as well as percent increment from baseline to 3 months in ferric-reducing ability of plasma (P = 0.003) were higher in the AO group compared with the PL group. Proportion of patients who had both reduced PDGF-AA and reduced pain was greater in AO as compared with PL group (17/31 vs 9/30, P = 0.05) CONCLUSIONS Reduction in markers of fibrosis (PDGF-AA) translated into clinical outcome (reduction in pain and analgesic requirements) in those supplemented with AOs in CP (trial registration, CTRI/2011/05/001747).
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Esrefoglu M. Experimental and clinical evidence of antioxidant therapy in acute pancreatitis. World J Gastroenterol 2012; 18:5533-41. [PMID: 23112545 PMCID: PMC3482639 DOI: 10.3748/wjg.v18.i39.5533] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2012] [Revised: 06/13/2012] [Accepted: 06/28/2012] [Indexed: 02/06/2023] Open
Abstract
Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery. In recent years, substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents. Some of these antioxidants have been found beneficial in the treatment of AP in humans; however, at present there is insufficient clinical data to support the benefits of antioxidants, alone or in combination with conventional therapy, in the management of AP in humans. Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species. Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP. Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants. The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP.
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Escobar J, Pereda J, López-Rodas G, Sastre J. Redox signaling and histone acetylation in acute pancreatitis. Free Radic Biol Med 2012; 52:819-37. [PMID: 22178977 DOI: 10.1016/j.freeradbiomed.2011.11.009] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2011] [Revised: 11/08/2011] [Accepted: 11/09/2011] [Indexed: 12/22/2022]
Abstract
Histone acetylation via CBP/p300 coordinates the expression of proinflammatory cytokines in the activation phase of inflammation, particularly through mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), and signal transducers and activators of transcription (STAT) pathways. In contrast, histone deacetylases (HDACs) and protein phosphatases are mainly involved in the attenuation phase of inflammation. The role of reactive oxygen species (ROS) in the inflammatory cascade is much more important than expected. Mitochondrial ROS act as signal-transducing molecules that trigger proinflammatory cytokine production via inflammasome-independent and inflammasome-dependent pathways. The major source of ROS in acute inflammation seems to be NADPH oxidases, whereas NF-κB, protein phosphatases, and HDACs are the major targets of ROS and redox signaling in this process. There is a cross-talk between oxidative stress and proinflammatory cytokines through serine/threonine protein phosphatases, tyrosine protein phosphatases, and MAPKs that greatly contributes to amplification of the uncontrolled inflammatory cascade and tissue injury in acute pancreatitis. Chromatin remodeling during induction of proinflammatory genes would depend primarily on phosphorylation of transcription factors and their binding to gene promoters together with recruitment of histone acetyltransferases. PP2A should be considered a key modulator of the inflammatory cascade in acute pancreatitis through the ERK/NF-κB pathway and histone acetylation.
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Affiliation(s)
- Javier Escobar
- Department of Physiology, School of Pharmacy, University of Valencia, Burjasot, Valencia, Spain
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Tandon RK, Garg PK. Oxidative stress in chronic pancreatitis: pathophysiological relevance and management. Antioxid Redox Signal 2011; 15:2757-66. [PMID: 21902596 DOI: 10.1089/ars.2011.4115] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
SIGNIFICANCE Chronic pancreatitis (CP) is a progressive, inflammatory disease of the pancreas leading to slow destruction of pancreatic parenchyma and progressive fibrosis. The pathophysiological mechanism of CP is not well understood. RECENT ADVANCES A pathophysiologic role of oxidative stress in CP has, however, been suggested in recent years. Pancreatic acinar cells contain phase I cytochrome P450 (CYP 450) biotransforming enzymes and phase II conjugation reactions for the metabolism of xenobiotics. The oxidative stress in the acinar cell may result from generation of free radicals through CYP induction, concurrent exposure to a chemical that undergoes bioactivation, and insufficiency of micronutrients that are required to sustain antioxidant (AO) capacity. CRITICAL ISSUES Studies have shown that there is indeed a state of oxidative stress as evidenced by increased levels of products of oxidative stress and reduced AO capacity in patients with CP. A recent randomized, controlled trial has shown beneficial effect of AO therapy in CP; a combination of AOs (0.54 g ascorbic acid, 9000 IU β-carotene, 270 IU α-tocopherol, 600 μg organic selenium, and 2 g methionine per day in divided doses) led to significant reductions in pain and oxidative stress in patients with CP. FUTURE DIRECTIONS Similar studies from other centers and multicenter studies should confirm that oxidative stress plays an important role in the pathophysiology of CP and supplementation with AOs leads to significant pain relief in patients with this disease.
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Affiliation(s)
- Rakesh Kumar Tandon
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
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Schnorr CE, Morrone MDS, Weber MH, Lorenzi R, Behr GA, Moreira JCF. The effects of vitamin A supplementation to rats during gestation and lactation upon redox parameters: increased oxidative stress and redox modulation in mothers and their offspring. Food Chem Toxicol 2011; 49:2645-54. [PMID: 21771631 DOI: 10.1016/j.fct.2011.07.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2010] [Revised: 06/19/2011] [Accepted: 07/06/2011] [Indexed: 11/25/2022]
Abstract
Vitamin A is an essential nutrient required in adequate amounts for reproduction and development. Subtle variations in the status of maternal nutrition may affect physiological and metabolic parameters in the fetus. Evidence suggests a key role for oxidative stress in these events. Literature is controversial about the effects of vitamin A supplementation. Here, we studied the effects of vitamin A supplementation on female Wistar rats during gestation and lactation on oxidative stress parameters of maternal and offspring tissues. Rats received daily doses of vitamin A at 2500, 12,500 and 25,000IU/kg. We observed an increase of oxidative damage markers in the reproductive tissues and plasma of dams. The activity of glutathione-S-transferase was modulated by vitamin A supplementation. It was found to be increased in the liver of dams and decreased in the kidneys of mothers and offspring. In pups, supplementation decreased the total antioxidant potential of the liver along with decreased superoxide dismutase/catalase activity ratio in the kidney. The levels of lipoperoxidation were increased in male offspring, but decreased in female pups. Collectively, the results suggest that excessive vitamin A intake during gestation and lactation might be toxic for mothers with adverse effects for the developing offspring.
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Affiliation(s)
- Carlos Eduardo Schnorr
- Centro de Estudos de Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
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Giustarini D, Dalle-Donne I, Tsikas D, Rossi R. Oxidative stress and human diseases: Origin, link, measurement, mechanisms, and biomarkers. Crit Rev Clin Lab Sci 2009; 46:241-81. [DOI: 10.3109/10408360903142326] [Citation(s) in RCA: 305] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Change of zinc, copper, and metallothionein concentrations and the copper-zinc superoxide dismutase activity in patients with pancreatitis. Pancreas 2009; 38:681-8. [PMID: 19629005 DOI: 10.1097/mpa.0b013e3181a53d1] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES The aims of the present studies were to measure the concentrations of zinc (Zn), copper (Cu), and metallothionein and the Cu/Zn superoxide dismutase activity as elements engaged in an essential manner in the prooxidative and antioxidative balance of organism and to demonstrate the degree to which metallothionein and Cu/Zn superoxide dismutase are involved in the inflammatory processes occurring in the pancreas. METHODS The concentration of metallothionein was measured by immunoenzymatic method. Serum Cu/Zn superoxide dismutase activity was determined using a commercial test. The measurements of Zn and Cu concentrations in serum were assessed with the use of flame atomic absorption spectrometry. RESULTS Lowered serum Zn concentration and higher Cu level were observed in the serum of patients with chronic exacerbated pancreatitis and chronic pancreatitis. The significant increase of metallothionein concentration and Cu/Zn superoxide dismutase activity was observed in the blood of patients with chronic exacerbated pancreatitis and chronic pancreatitis. In slices of the pancreas during pancreatitis, we observed in immunohistochemical reaction the variable involvement of Cu/Zn superoxide dismutase and metallothionein. CONCLUSIONS The results presented in these studies indicate an essential and variable involvement of antioxidants such Cu/Zn superoxide dismutase and metallothionein and disordered Cu and Zn homeostasis depending on the progression of inflammatory processes in patients with pancreatitis.
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Abstract
Reactive oxygen and reactive nitrogen species (ROS/RNS) have been implicated in the pathogenesis of acute and chronic pancreatitis. Clinical and basic science studies have indicated that ROS/RNS formation processes are intimately linked to the development of the inflammatory disorders. The detrimental effects of highly reactive ROS/RNS are mediated by their direct actions on biomolecules (lipids, proteins, and nucleic acids) and activation of proinflammatory signal cascades, which subsequently lead to activation of immune responses. The present article summarizes the possible sources of ROS/RNS formation and the detailed signaling cascades implicated in the pathogenesis of pancreatic inflammation, as observed in acute and chronic pancreatitis. A therapeutic ROS/RNS-scavenging strategy has been advocated for decades; however, clinical studies examining such approaches have been inconsistent in their results. Emerging evidence indicates that pancreatitis-inducing ROS/RNS generation may be attenuated by targeting ROS/RNS-generating enzymes and upstream mediators.
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Affiliation(s)
- Po Sing Leung
- Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
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Petrov MS, Gordetzov AS, Emelyanov NV. USEFULNESS OF INFRARED SPECTROSCOPY IN DIAGNOSIS OF ACUTE PANCREATITIS. ANZ J Surg 2007; 77:347-51. [PMID: 17497973 DOI: 10.1111/j.1445-2197.2007.04057.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The lack of a gold standard for the diagnosis of acute pancreatitis remains a problem. Our aim was to evaluate whether infrared spectroscopy of serum can establish the diagnosis of acute pancreatitis. METHODS Sixty-four patients with acute pancreatitis, 112 patients with non-pancreatic acute abdomen and 40 healthy subjects were studied. In addition to serum infrared spectral analysis, serum concentrations of amylase and lipase were measured on admission. RESULTS Infrared spectroscopy based on serum absorption patterns in the range 800-1000 nm successfully distinguished acute pancreatitis from acute abdominal disorders of extrapancreatic origin and from control specimens. The sensitivity, specificity and positive and negative predictive values of infrared spectroscopy on admission were 91, 91, 85, and 94%, respectively. Within 24 h of onset of symptoms, infrared spectroscopy, lipase and amylase showed similar areas under the ROC curves for infrared spectra of serum (0.93), lipase (0.96) and amylase (0.91). CONCLUSIONS The successful classification of infrared spectra in patients with acute pancreatitis implies that the pathophysiology of disease alters the composition of the specimen in a characteristic fashion--in this case the serum make-up reflects the presence of acute pancreatitis.
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Affiliation(s)
- Maxim S Petrov
- Department of Surgery, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.
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