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Avi A. Weinbroum - One of the best experts on this subject based on the ideXlab platform.
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Methylene Blue Attenuates Pancreas Ischemia–Reperfusion (IR)-Induced Lung Injury: A Dose Response Study in a Rat Model
Journal of Gastrointestinal Surgery, 2009Co-Authors: Avi A. WeinbroumAbstract:Background Oxidants (and their generator, xanthine oxidase [XO]) play a role in inducing acute lung Injury (ALI) expressed both structurally and functionally. Such damage has recently been demonstrated in the presence of Pancreas ischemia–reperfusion (IR). We now investigated whether methylene blue (MB), a clinically used coloring agent and antioxidant in itself, protected the lung exposed to Pancreas IR. Materials and Methods Isolated pancreata (eight replicates/group) were (1) continuously perfused (controls), (2) made ischemic (IR-0) for 40 min and reperfused without treatment, (3) organs procured from allopurinol-treated rats made ischemic and reperfused with allopurinol, and (4) made ischemic and treated upon reperfusion with three different doses of MB contained in the perfusate. All perfusate solutions were directed into the isolated lungs’ circulation whereby they were perfused for 60 min. Results Pancreas Injury was documented in all IR organs by abnormally high reperfusion pressure, wet-to-dry ratio, amylase and lipase concentrations, and abnormal XO activity and reduced glutathione in the circulation. Lungs paired with IR-0 pancreata developed ∼60% increase in ventilatory plateau pressure and final P o _2/Fi o _2 decrease by 35%. Their weight during reperfusion and bronchoalveolar lavage (BAL) volume and contents increased 1.5–2.5 times the normal values; XO and reduced glutathione values were abnormal both in the BAL and in the lung tissues. Lungs exposed to IR effluents containing allopurinol or 68 μM MB were minimally damaged, whereas perfusion solutions containing 42 or 128 μM MB were ineffective in preventing lung Injury. Conclusions Ex vivo Pancreas IR-induced ALI is preventable by MB, although at a narrow dose range.
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Mannitol Prevents Acute Lung Injury After Pancreas Ischemia-Reperfusion: A Dose-Response, Ex Vivo Study
Lung, 2009Co-Authors: Avi A. WeinbroumAbstract:Oxidants and their generator, xanthine oxidase (XO), play a major role in the damaging of the structural and functional integrity of the lung. Such damage has been recently demonstrated in the presence of Pancreas ischemia–reperfusion (IR). We investigated whether mannitol, a clinically used agent and antioxidant, prevented lung damage after Pancreas IR. Rats ( n = 48) were anesthetized, after which each Pancreas was isolated and perfused (controls), or made ischemic (IR) for 40 min, or made ischemic and treated upon reperfusion with four different doses of mannitol administered in the perfusate (8 replicates/group). Ischemia was followed by in-series 15-min Pancreas plus normal isolated lung reperfusion. Isolated lungs were subsequently perfused for 45 min with the 15-min accumulated effluents. Pancreas Injury occurred in all IR organs as demonstrated by abnormal reperfusion pressure, the wet-to-dry ratio, amylase and lipase leakage into the circulation, and XO activity and reduced glutathione (GSH) pool in the tissues. Pulmonary plateau pressure increased by 80%, and final P o _2/Fi o _2 decreased by 28% in the IR-untreated paired lungs. Bronchoalveolar lavage volume increased by 50% and 2- to 8-fold increase in their contained XO and GSH were recorded as well. The above indices of Injury in lungs perfused with 0.77 mM mannitol were the least detected, compared with negligible efficacy of other (0.55
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methylene blue attenuates Pancreas ischemia reperfusion ir induced lung Injury a dose response study in a rat model
Journal of Gastrointestinal Surgery, 2009Co-Authors: Avi A. WeinbroumAbstract:Background Oxidants (and their generator, xanthine oxidase [XO]) play a role in inducing acute lung Injury (ALI) expressed both structurally and functionally. Such damage has recently been demonstrated in the presence of Pancreas ischemia–reperfusion (IR). We now investigated whether methylene blue (MB), a clinically used coloring agent and antioxidant in itself, protected the lung exposed to Pancreas IR. Materials and Methods Isolated pancreata (eight replicates/group) were (1) continuously perfused (controls), (2) made ischemic (IR-0) for 40 min and reperfused without treatment, (3) organs procured from allopurinol-treated rats made ischemic and reperfused with allopurinol, and (4) made ischemic and treated upon reperfusion with three different doses of MB contained in the perfusate. All perfusate solutions were directed into the isolated lungs’ circulation whereby they were perfused for 60 min. Results Pancreas Injury was documented in all IR organs by abnormally high reperfusion pressure, wet-to-dry ratio, amylase and lipase concentrations, and abnormal XO activity and reduced glutathione in the circulation. Lungs paired with IR-0 pancreata developed ∼60% increase in ventilatory plateau pressure and final PO2/FiO2 decrease by 35%. Their weight during reperfusion and bronchoalveolar lavage (BAL) volume and contents increased 1.5–2.5 times the normal values; XO and reduced glutathione values were abnormal both in the BAL and in the lung tissues. Lungs exposed to IR effluents containing allopurinol or 68 μM MB were minimally damaged, whereas perfusion solutions containing 42 or 128 μ MM B were ineffective in preventing lung Injury. Conclusions Ex vivo Pancreas IR-induced ALI is preventable by MB, although at a narrow dose range.
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mannitol prevents acute lung Injury after Pancreas ischemia reperfusion a dose response ex vivo study
Lung, 2009Co-Authors: Avi A. WeinbroumAbstract:Oxidants and their generator, xanthine oxidase (XO), play a major role in the damaging of the structural and functional integrity of the lung. Such damage has been recently demonstrated in the presence of Pancreas ische- mia-reperfusion (IR). We investigated whether mannitol, a clinically used agent and antioxidant, prevented lung damage after Pancreas IR. Rats (n = 48) were anesthe- tized, after which each Pancreas was isolated and perfused (controls), or made ischemic (IR) for 40 min, or made ischemic and treated upon reperfusion with four different doses of mannitol administered in the perfusate (8 repli- cates/group). Ischemia was followed by in-series 15-min Pancreas plus normal isolated lung reperfusion. Isolated lungs were subsequently perfused for 45 min with the 15- min accumulated effluents. Pancreas Injury occurred in all IR organs as demonstrated by abnormal reperfusion pres- sure, the wet-to-dry ratio, amylase and lipase leakage into the circulation, and XO activity and reduced glutathione (GSH) pool in the tissues. Pulmonary plateau pressure increased by 80%, and final PO2/FiO2 decreased by 28% in the IR-untreated paired lungs. Bronchoalveolar lavage volume increased by 50% and 2- to 8-fold increase in their contained XO and GSH were recorded as well. The above indices of Injury in lungs perfused with 0.77 mM mannitol were the least detected, compared with negligible efficacy of other (0.55 \ 0.22 \ 1.1 mM) dosages. Amylase and lipase did not contribute to lung Injury. Ex vivo acute pancreatitis induces acute lung Injury via oxidants/antiox- idants imbalance, which is preventable by mannitol.
Salvatore Cuzzocrea - One of the best experts on this subject based on the ideXlab platform.
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The cyclopentenone prostaglandin 15-deoxyΔ^12,14-prostaglandin J_2 attenuates the development of zymosan-induced shock
Intensive Care Medicine, 2005Co-Authors: Stefania Marzocco, Emanuela Mazzon, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Giuseppina Autore, Salvatore CuzzocreaAbstract:Objective Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-Δ^12,14-PGJ_2 (15d-PGJ_2), a PPAR-γ ligand, in a model of zymosan-induced nonseptic shock in mice. Materials and methods Mice were randomly assigned to one of four groups ( n =10 each) and treated i.p. as follows: group 1, zymosan (500 mg/kg suspended in saline solution) and vehicle (10% DMSO); group 2, zymosan (500 mg/kg suspended in saline solution) plus 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO; group 4, vehicle for PGJ_2 (10% DMSO) always 1 h before and 6 h after saline administration. After 18 h mice were killed and tissues and biological fluids used for biochemical, immunohistochemical, and histological analysis. Measurements and results 15d-PGJ_2 inhibited the inflammatory response and significantly reduced peritoneal mononuclear cell infiltration and histological Injury in mice. A significant protection was demonstrated in kidney, liver, and Pancreas Injury by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubin, and alkaline phosphatase levels. 15d-PGJ_2 also reduced the appearance of nitrotyrosine in the inflamed intestinal tissues. Histological examination revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ_2 treated mice. Conclusions Our findings demonstrate that 15d-PGJ_2 exerts potent anti-inflammatory effects on zymosan-induced shock.
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Calpain I inhibitor ameliorates the indices of disease severity in a murine model of cerulein-induced acute pancreatitis
Intensive Care Medicine, 2004Co-Authors: Ioannis Virlos, Emanuela Mazzon, Rosanna Di Paola, Tiziana Genovese, Ivana Serraino, Christoph Thiemerman, Ajith Siriwardena, Salvatore CuzzocreaAbstract:Objective Nuclear factor-κB (NF-κB) is a transcription factor which plays a pivotal role in the induction of genes involved in the response to Injury and inflammation. Calpain I inhibitor is a potent antioxidant which is an effective inhibitor of NF-κB. This study examined whether the postulate that calpain I inhibitor attenuates experimental acute pancreatitis. Design and setting In a murine model we measured NF-κB activation, expression of intercellular adhesion molecule (ICAM) 1, nitrotyrosine, inducible nitric oxide synthase (iNOS), nuclear enzyme poly(ADP-ribose) synthetase (PARS), myeloperoxidase, malondialdehyde, amylase and lipase and determined histological evidence of lung and Pancreas Injury in four groups: control (saline only), cerulein, calpain I inhibitor plus cerulein and calpain I inhibitor plus saline. Measurements and results Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterised by oedema, neutrophil infiltration, tissue haemorrhage and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine, iNOS and PARS in the Pancreas and lung of cerulein-treated mice. In contrast, pre-treatment with calpain I inhibitor markedly reduced: the degree of Pancreas and lung Injury; upregulation/expression of ICAM-1; staining for iNOS, nitrotyrosine and PARS; and lipid peroxidation. Additionally, calpain I inhibitor treatment significantly prevented the activation of NF-κB as suggested by the inhibition of IκB-α; degradation in the Pancreas tissues after cerulein administration. Conclusions Taken together, our results clearly demonstrate that prevention of the activation of NF-κB by calpain I inhibitor ameliorates experimental murine acute pancreatitis.
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Methylguanidine reduces the development of non septic shock induced by zymosan in mice.
Life Sciences, 2004Co-Authors: Stefania Marzocco, Salvatore Cuzzocrea, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Raffaella Sorrentino, Giuseppe Scollo, Giuseppina AutoreAbstract:In the present study we evaluate the effect of methylguanidine (MG), a product of protein catabolism, in a model of acute inflammation (zymosan induced inflammation) in mice where oxyradical and nitric oxide (NO) play a crucial role. Our data show that MG, given intraperitoneally at the dose of 30 mg/Kg, inhibits the inflammatory response reducing significantly (P < 0.05) peritoneal exudates formation, mononuclear cell infiltration and histological Injury in mice. Furthermore, our data suggests that there is a significant (P < 0.05) reduction in kidney, liver and Pancreas Injury as demonstrated by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubine and alkaline phosfatase levels. MG is also able to reduce the appearance of nitrotyrosine and of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) synthase (PARS) immunoreactivity in the inflamed intestinal and lung tissues. The histological examination revealed a significant reduction in zymosan-induced intestinal and lung damage in MG-treated mice. Taken together, the present results demonstrate that MG exerts potent anti-inflammatory effects on zymosan-induced shock.
Mohammad Tabarestani - One of the best experts on this subject based on the ideXlab platform.
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The predictive role of amylase and lipase levels on Pancreas Injury diagnosis in patients with blunt abdominal trauma.
Hormone Molecular Biology and Clinical Investigation, 2020Co-Authors: Seyed Mohammad Hosseininejad, Farzad Bozorgi, Touraj Assadi, Seyyed Hosein Montazar, Fatemeh Jahanian, Vahid Hoseini, Mahboobeh Shamsaee, Mohammad TabarestaniAbstract:Objectives Despite the low incidence of pancreatic Injury in the abdominal blunt trauma (BTA), its early diagnosis is very important; since pancreatic Injury is associated with high rates of morbidity and mortality. However, due to the high association of pancreatic Injury with Injury of other abdominal organs, its diagnosis may be delayed and complicated. The use of imaging modalities is also subject to limitations for reasons such as cost, unavailability, and harmfulness. Consequently, the present study aimed to investigate the predictive role of amylase and lipase enzyme levels in the final diagnosis of pancreatic Injury in patients with BTA. Methods In a prospective diagnostic study, 384 patients with BTA referring to Imam Khomeini hospital of Sari (north of Iran) were enrolled according to the inclusion and exclusion criteria. Initial patient data including age and sex were recorded. Blood samples were analyzed in the laboratory to measure complete blood count (CBC), amylase and lipase enzyme levels. Patients were followed up during hospitalization and focal ultrasound for abdominal trauma (FAST), CT-Scan and laparotomy results were recorded. Finally, the data was analyzed using SPSS version 22. Results The level of amylase enzyme was significantly higher in males (p = 0.04), but the level of lipase enzyme was not significantly different between two genders (p > 0.05). The most common symptoms and signs in patients were pain, tenderness, and hematoma, respectively. The frequency of pancreatic Injury in all patients with blunt abdominal trauma was 7.5% based of FAST, 7% based on CT-Scan and 12.4% based on laparotomy. Comparison of laboratory findings based on FAST, CT-Scan and laparotomy results showed that the level of amylase and lipase enzymes in patients with internal organ and pancreatic damage were higher than in patients without internal organ Injury (p 0.05). However, comparison of laboratory findings based on CT-Scan and laparotomy results showed a significant increase in the level of amylase and lipase enzymes in patients with pancreatic trauma compared to patients with Injury of other organs (p
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the predictive role of amylase and lipase levels on Pancreas Injury diagnosis in patients with blunt abdominal trauma
Hormone Molecular Biology and Clinical Investigation, 2020Co-Authors: Seyed Mohammad Hosseininejad, Farzad Bozorgi, Touraj Assadi, Seyyed Hosein Montazar, Fatemeh Jahanian, Vahid Hoseini, Mahboobeh Shamsaee, Mohammad TabarestaniAbstract:Objectives Despite the low incidence of pancreatic Injury in the abdominal blunt trauma (BTA), its early diagnosis is very important; since pancreatic Injury is associated with high rates of morbidity and mortality. However, due to the high association of pancreatic Injury with Injury of other abdominal organs, its diagnosis may be delayed and complicated. The use of imaging modalities is also subject to limitations for reasons such as cost, unavailability, and harmfulness. Consequently, the present study aimed to investigate the predictive role of amylase and lipase enzyme levels in the final diagnosis of pancreatic Injury in patients with BTA. Methods In a prospective diagnostic study, 384 patients with BTA referring to Imam Khomeini hospital of Sari (north of Iran) were enrolled according to the inclusion and exclusion criteria. Initial patient data including age and sex were recorded. Blood samples were analyzed in the laboratory to measure complete blood count (CBC), amylase and lipase enzyme levels. Patients were followed up during hospitalization and focal ultrasound for abdominal trauma (FAST), CT-Scan and laparotomy results were recorded. Finally, the data was analyzed using SPSS version 22. Results The level of amylase enzyme was significantly higher in males (p = 0.04), but the level of lipase enzyme was not significantly different between two genders (p > 0.05). The most common symptoms and signs in patients were pain, tenderness, and hematoma, respectively. The frequency of pancreatic Injury in all patients with blunt abdominal trauma was 7.5% based of FAST, 7% based on CT-Scan and 12.4% based on laparotomy. Comparison of laboratory findings based on FAST, CT-Scan and laparotomy results showed that the level of amylase and lipase enzymes in patients with internal organ and pancreatic damage were higher than in patients without internal organ Injury (p 0.05). However, comparison of laboratory findings based on CT-Scan and laparotomy results showed a significant increase in the level of amylase and lipase enzymes in patients with pancreatic trauma compared to patients with Injury of other organs (p < 0.001). Conclusions The results of this study showed that pancreatic Injury in blunt trauma is associated with a significant increase in levels of amylase and lipase enzymes. In addition, an increase in levels of amylase and lipase enzymes is associated with internal organ damage. Serum amylase and lipase levels can be used as useful biomarkers to decide whether to perform CT-Scan or laparotomy.
Tiziana Genovese - One of the best experts on this subject based on the ideXlab platform.
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The cyclopentenone prostaglandin 15-deoxyΔ^12,14-prostaglandin J_2 attenuates the development of zymosan-induced shock
Intensive Care Medicine, 2005Co-Authors: Stefania Marzocco, Emanuela Mazzon, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Giuseppina Autore, Salvatore CuzzocreaAbstract:Objective Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-Δ^12,14-PGJ_2 (15d-PGJ_2), a PPAR-γ ligand, in a model of zymosan-induced nonseptic shock in mice. Materials and methods Mice were randomly assigned to one of four groups ( n =10 each) and treated i.p. as follows: group 1, zymosan (500 mg/kg suspended in saline solution) and vehicle (10% DMSO); group 2, zymosan (500 mg/kg suspended in saline solution) plus 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO; group 4, vehicle for PGJ_2 (10% DMSO) always 1 h before and 6 h after saline administration. After 18 h mice were killed and tissues and biological fluids used for biochemical, immunohistochemical, and histological analysis. Measurements and results 15d-PGJ_2 inhibited the inflammatory response and significantly reduced peritoneal mononuclear cell infiltration and histological Injury in mice. A significant protection was demonstrated in kidney, liver, and Pancreas Injury by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubin, and alkaline phosphatase levels. 15d-PGJ_2 also reduced the appearance of nitrotyrosine in the inflamed intestinal tissues. Histological examination revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ_2 treated mice. Conclusions Our findings demonstrate that 15d-PGJ_2 exerts potent anti-inflammatory effects on zymosan-induced shock.
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Calpain I inhibitor ameliorates the indices of disease severity in a murine model of cerulein-induced acute pancreatitis
Intensive Care Medicine, 2004Co-Authors: Ioannis Virlos, Emanuela Mazzon, Rosanna Di Paola, Tiziana Genovese, Ivana Serraino, Christoph Thiemerman, Ajith Siriwardena, Salvatore CuzzocreaAbstract:Objective Nuclear factor-κB (NF-κB) is a transcription factor which plays a pivotal role in the induction of genes involved in the response to Injury and inflammation. Calpain I inhibitor is a potent antioxidant which is an effective inhibitor of NF-κB. This study examined whether the postulate that calpain I inhibitor attenuates experimental acute pancreatitis. Design and setting In a murine model we measured NF-κB activation, expression of intercellular adhesion molecule (ICAM) 1, nitrotyrosine, inducible nitric oxide synthase (iNOS), nuclear enzyme poly(ADP-ribose) synthetase (PARS), myeloperoxidase, malondialdehyde, amylase and lipase and determined histological evidence of lung and Pancreas Injury in four groups: control (saline only), cerulein, calpain I inhibitor plus cerulein and calpain I inhibitor plus saline. Measurements and results Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterised by oedema, neutrophil infiltration, tissue haemorrhage and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine, iNOS and PARS in the Pancreas and lung of cerulein-treated mice. In contrast, pre-treatment with calpain I inhibitor markedly reduced: the degree of Pancreas and lung Injury; upregulation/expression of ICAM-1; staining for iNOS, nitrotyrosine and PARS; and lipid peroxidation. Additionally, calpain I inhibitor treatment significantly prevented the activation of NF-κB as suggested by the inhibition of IκB-α; degradation in the Pancreas tissues after cerulein administration. Conclusions Taken together, our results clearly demonstrate that prevention of the activation of NF-κB by calpain I inhibitor ameliorates experimental murine acute pancreatitis.
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Methylguanidine reduces the development of non septic shock induced by zymosan in mice.
Life Sciences, 2004Co-Authors: Stefania Marzocco, Salvatore Cuzzocrea, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Raffaella Sorrentino, Giuseppe Scollo, Giuseppina AutoreAbstract:In the present study we evaluate the effect of methylguanidine (MG), a product of protein catabolism, in a model of acute inflammation (zymosan induced inflammation) in mice where oxyradical and nitric oxide (NO) play a crucial role. Our data show that MG, given intraperitoneally at the dose of 30 mg/Kg, inhibits the inflammatory response reducing significantly (P < 0.05) peritoneal exudates formation, mononuclear cell infiltration and histological Injury in mice. Furthermore, our data suggests that there is a significant (P < 0.05) reduction in kidney, liver and Pancreas Injury as demonstrated by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubine and alkaline phosfatase levels. MG is also able to reduce the appearance of nitrotyrosine and of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) synthase (PARS) immunoreactivity in the inflamed intestinal and lung tissues. The histological examination revealed a significant reduction in zymosan-induced intestinal and lung damage in MG-treated mice. Taken together, the present results demonstrate that MG exerts potent anti-inflammatory effects on zymosan-induced shock.
Rosanna Di Paola - One of the best experts on this subject based on the ideXlab platform.
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The cyclopentenone prostaglandin 15-deoxyΔ^12,14-prostaglandin J_2 attenuates the development of zymosan-induced shock
Intensive Care Medicine, 2005Co-Authors: Stefania Marzocco, Emanuela Mazzon, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Giuseppina Autore, Salvatore CuzzocreaAbstract:Objective Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-Δ^12,14-PGJ_2 (15d-PGJ_2), a PPAR-γ ligand, in a model of zymosan-induced nonseptic shock in mice. Materials and methods Mice were randomly assigned to one of four groups ( n =10 each) and treated i.p. as follows: group 1, zymosan (500 mg/kg suspended in saline solution) and vehicle (10% DMSO); group 2, zymosan (500 mg/kg suspended in saline solution) plus 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO; group 4, vehicle for PGJ_2 (10% DMSO) always 1 h before and 6 h after saline administration. After 18 h mice were killed and tissues and biological fluids used for biochemical, immunohistochemical, and histological analysis. Measurements and results 15d-PGJ_2 inhibited the inflammatory response and significantly reduced peritoneal mononuclear cell infiltration and histological Injury in mice. A significant protection was demonstrated in kidney, liver, and Pancreas Injury by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubin, and alkaline phosphatase levels. 15d-PGJ_2 also reduced the appearance of nitrotyrosine in the inflamed intestinal tissues. Histological examination revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ_2 treated mice. Conclusions Our findings demonstrate that 15d-PGJ_2 exerts potent anti-inflammatory effects on zymosan-induced shock.
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Calpain I inhibitor ameliorates the indices of disease severity in a murine model of cerulein-induced acute pancreatitis
Intensive Care Medicine, 2004Co-Authors: Ioannis Virlos, Emanuela Mazzon, Rosanna Di Paola, Tiziana Genovese, Ivana Serraino, Christoph Thiemerman, Ajith Siriwardena, Salvatore CuzzocreaAbstract:Objective Nuclear factor-κB (NF-κB) is a transcription factor which plays a pivotal role in the induction of genes involved in the response to Injury and inflammation. Calpain I inhibitor is a potent antioxidant which is an effective inhibitor of NF-κB. This study examined whether the postulate that calpain I inhibitor attenuates experimental acute pancreatitis. Design and setting In a murine model we measured NF-κB activation, expression of intercellular adhesion molecule (ICAM) 1, nitrotyrosine, inducible nitric oxide synthase (iNOS), nuclear enzyme poly(ADP-ribose) synthetase (PARS), myeloperoxidase, malondialdehyde, amylase and lipase and determined histological evidence of lung and Pancreas Injury in four groups: control (saline only), cerulein, calpain I inhibitor plus cerulein and calpain I inhibitor plus saline. Measurements and results Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterised by oedema, neutrophil infiltration, tissue haemorrhage and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine, iNOS and PARS in the Pancreas and lung of cerulein-treated mice. In contrast, pre-treatment with calpain I inhibitor markedly reduced: the degree of Pancreas and lung Injury; upregulation/expression of ICAM-1; staining for iNOS, nitrotyrosine and PARS; and lipid peroxidation. Additionally, calpain I inhibitor treatment significantly prevented the activation of NF-κB as suggested by the inhibition of IκB-α; degradation in the Pancreas tissues after cerulein administration. Conclusions Taken together, our results clearly demonstrate that prevention of the activation of NF-κB by calpain I inhibitor ameliorates experimental murine acute pancreatitis.
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Methylguanidine reduces the development of non septic shock induced by zymosan in mice.
Life Sciences, 2004Co-Authors: Stefania Marzocco, Salvatore Cuzzocrea, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Raffaella Sorrentino, Giuseppe Scollo, Giuseppina AutoreAbstract:In the present study we evaluate the effect of methylguanidine (MG), a product of protein catabolism, in a model of acute inflammation (zymosan induced inflammation) in mice where oxyradical and nitric oxide (NO) play a crucial role. Our data show that MG, given intraperitoneally at the dose of 30 mg/Kg, inhibits the inflammatory response reducing significantly (P < 0.05) peritoneal exudates formation, mononuclear cell infiltration and histological Injury in mice. Furthermore, our data suggests that there is a significant (P < 0.05) reduction in kidney, liver and Pancreas Injury as demonstrated by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubine and alkaline phosfatase levels. MG is also able to reduce the appearance of nitrotyrosine and of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) synthase (PARS) immunoreactivity in the inflamed intestinal and lung tissues. The histological examination revealed a significant reduction in zymosan-induced intestinal and lung damage in MG-treated mice. Taken together, the present results demonstrate that MG exerts potent anti-inflammatory effects on zymosan-induced shock.
