scholarly journals Pre-inhalation of hydrogen-rich gases protect against caerulein-induced mouse acute pancreatitis while enhance the pancreatic Hsp60 protein expression

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kun Li ◽  
Hongling Yin ◽  
Yi Duan ◽  
Peizhen Lai ◽  
Yancheng Cai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Protein Expression ◽  
Protective Effect ◽  
Pancreatic Enzymes ◽  
Pancreatic Acinar Cells ◽  
Targeted Prevention ◽  
Heat Shock Protein 60 ◽  
Hydrogen Pretreatment ◽  
Hsp60 Protein

Abstract Background Acute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. Aim of this study was to investigate effect of hydrogen pretreatment on AP and the mechanisms, focusing on pancreatic oxidative stress and Hsp60 expression. Methods 80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1 h, 3 h and 5 h (n = 6–8). Mouse AP model was induced by intraperitoneal injection of 50 μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance. Results The pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1 h and 5 h. Conclusions Pre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.

scholarly journals Pre-inhalation of hydrogen-rich gases protect against caerulein-induced mouse acute pancreatitis while enhance the pancreatic Hsp60 protein expression

2020 ◽  
Author(s):  
Kun Li ◽  
Hongling Yin ◽  
Yi Duan ◽  
Peizhen Lai ◽  
Yanchen Cai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Protein Expression ◽  
Protective Effect ◽  
Pancreatic Enzymes ◽  
Pancreatic Acinar Cells ◽  
Targeted Prevention ◽  
Heat Shock Protein 60 ◽  
Hydrogen Pretreatment ◽  
Hsp60 Protein

Abstract Background: Acute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. Aim of this study was to investigate effect of hydrogen pretreatment on AP and the mechanisms, focusing on pancreatic oxidative stress and Hsp60.Methods: 80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1h, 3h and 5h (n=6- 8). Mouse AP model was induced by intraperitoneal injection of 50μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance.Results: The pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1h and 5h. Conclusions: Pre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.

scholarly journals Pre-inhalation of Hydrogen-rich Gases Protect Against Caerulein-induced Mouse Acute Pancreatitis While Enhance the Pancreatic Hsp60 Protein Expression

2020 ◽  
Author(s):  
Kun Li ◽  
Hongling Yin ◽  
Yi Duan ◽  
Peizhen Lai ◽  
Yanchen Cai ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Protein Expression ◽  
Protective Effect ◽  
Observation Time ◽  
Pancreatic Enzymes ◽  
Pancreatic Acinar Cells ◽  
Targeted Prevention ◽  
Heat Shock Protein 60 ◽  
Hydrogen Pretreatment ◽  
Hsp60 Protein

Abstract Background: Acute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. The aim of this study was to investigate effect of hydrogen pretreatment on experimental AP mice, as well as the possible mechanisms, focusing on antioxidant and Hsp60 expression alteration mechanisms.Methods: 80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1h, 3h and 5h (n=6- 8). Mouse AP model was induced by intraperitoneal injection of 50μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance.Results: The pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1h and 5h. Conclusions: Pre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.

scholarly journals Docosahexaenoic Acid Induces Expression of NAD(P)H: Quinone Oxidoreductase and Heme Oxygenase-1 through Activation of Nrf2 in Cerulein-Stimulated Pancreatic Acinar Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1084
Author(s):  
Yu Jin Ahn ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Docosahexaenoic Acid ◽  
Heme Oxygenase ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Heme Oxygenase 1 ◽  
Omega 3 ◽  
Quinone Oxidoreductase ◽  
Ar42j Cells

Oxidative stress is a major risk factor for acute pancreatitis. Reactive oxygen species (ROS) mediate expression of inflammatory cytokines such as interleukin-6 (IL-6) which reflects the severity of acute pancreatitis. The nuclear factor erythroid-2-related factor 2 (Nrf2) pathway is activated to induce the expression of antioxidant enzymes such as NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) as a cytoprotective response to oxidative stress. In addition, binding of Kelch-like ECH-associated protein 1 (Keap1) to Nrf2 promotes degradation of Nrf2. Docosahexaenoic acid (DHA)—an omega-3 fatty acid—exerts anti-inflammatory and antioxidant effects. Oxidized omega-3 fatty acids react with Keap1 to induce Nrf2-regulated gene expression. In this study, we investigated whether DHA reduces ROS levels and inhibits IL-6 expression via Nrf2 signaling in pancreatic acinar (AR42J) cells stimulated with cerulein, as an in vitro model of acute pancreatitis. The cells were pretreated with or without DHA for 1 h and treated with cerulein (10−8 M) for 1 (ROS levels, protein levels of NQO1, HO-1, pNrf2, Nrf2, and Keap1), 6 (IL-6 mRNA expression), and 24 h (IL-6 protein level in the medium). Our results showed that DHA upregulates the expression of NQO1 and HO-1 in cerulein-stimulated AR42J cells by promoting phosphorylation and nuclear translocation of Nrf2. DHA increased interaction between Keap1 and Nrf2 in AR42J cells, which may increase Nrf2 activity by inhibiting Keap1-mediated sequestration of Nrf2. In addition, DHA-induced expression of NQO1 and HO-1 is related to reduction of ROS and IL-6 levels in cerulein-stimulated AR42J cells. In conclusion, DHA inhibits ROS-mediated IL-6 expression by upregulating Nrf2-mediated expression of NQO1 and HO-1 in cerulein-stimulated pancreatic acinar cells. DHA may exert positive modulatory effects on acute pancreatitis by inhibiting oxidative stress and inflammatory cytokine production by activating Nrf2 signaling in pancreatic acinar cells.

scholarly journals Desoxyrhapontigenin attenuates neuronal apoptosis in an isoflurane-induced neuronal injury model by modulating the TLR-4/cyclin B1/Sirt-1 pathway

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Feng Liang ◽  
Xin Fu ◽  
Yunpengfei Li ◽  
Fanglei Han
Keyword(s):  
Oxidative Stress ◽  
Cognitive Function ◽  
Protein Expression ◽  
Protective Effect ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuronal Injury ◽  
Cyclin B1 ◽  
The Brain ◽  
And Oxidative Stress

Abstract This study investigated the protective effect of desoxyrhapontigenin (DOP) against isoflurane (ISF)-induced neuronal injury in rats. Neuronal injury was induced in pups by exposing them to 0.75% ISF on postnatal day 7 with 30% oxygen for 6 h. The pups were treated with DOP 10 mg/kg, i.p., for 21 days after ISF exposure. The protective effect of DOP was estimated by assessing cognitive function using the neurological score and the Morris water maze. Neuronal apoptosis was assessed in the hippocampus using the TUNEL assay, and protein expression of caspase-3, Bax, and Bcl-2 was measured by Western blotting. The levels of cytokines and oxidative stress parameters were assessed by ELISA. Western blotting and RT-PCR were performed to measure the expression of NF-kB, TLR-4, Sirt-1, and cyclin B1 protein in the brain. The cognitive function and neurological function scores were improved in the DOP group compared with the ISF group. Moreover, DOP treatment reduced the number of TUNEL-positive cells and the expression of caspase-3, Bax, and Bcl-2 protein in the brains of rats with neuronal injury. The levels of mediators of inflammation and oxidative stress were reduced in the brain tissue of the DOP group. Treatment with DOP attenuated the protein expression of TLR-4, NF-kB, cyclin B1, and Sirt-1 in the brain tissue of rats with neuronal injury. In conclusion, DOP ameliorates neuronal apoptosis and improves cognitive function in rats with ISF-induced neuronal injury. Moreover, DOP treatment can prevent neuronal injury by regulating the TLR-4/cyclin B1/Sirt-1 pathway.

scholarly journals The role of intracellular Ca2+ signaling in the exocrine pancreatic damage during acute pancreatitis

2020 ◽  
Author(s):  
Júlia Fanczal
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Bile Acid ◽  
Bile Acids ◽  
Digestive Enzyme ◽  
Acinar Cells ◽  
Mitochondrial Damage ◽  
Enzyme Activation ◽  
Pancreatic Acinar Cells ◽  
Biliary Pancreatitis

Acute biliary pancreatitis poses a significant clinical challenge as currently no specific pharmaceutical treatment exists. Disturbed intracellular Ca2+ signalling caused by bile acids is a hallmark of the disease, which induces increased reactive oxygen species (ROS) production, mitochondrial damage, intra-acinar digestive enzyme activation and cell death. Because of this mechanism of action, prevention of toxic cellular Ca2+ overload is a promising therapeutic target. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca2+ overload across different diseases. However, the expression and possible functions of TRPM2 in the exocrine pancreas remain unknown. Here we found that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar, which can be activated by increased oxidative stress induced by H2O2 treatment. TRPM2 activity was found to contribute to bile acid-induced extracellular Ca2+ influx in acinar cells. The generation of intracellular ROS in response to bile acids was remarkably higher in pancreatic acinar cells. This activity promoted acinar cell necrosis in vitro independently from mitochondrial damage or mitochondrial fragmentation. In addition, bile-acid-induced experimental pancreatitis was less severe in TRPM2 knockout mice, whereas the lack of TRPM2 had no protective effect in cerulein-induced acute pancreatitis. Our results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.

HSP60 Predicts Survival in Advanced Serous Ovarian Cancer

2013 ◽  
Vol 23 (3) ◽  
pp. 448-455 ◽  
Author(s):  
Elisabet Hjerpe ◽  
Suzanne Egyhazi ◽  
Joseph Carlson ◽  
Marianne Frostvik Stolt ◽  
Kjell Schedvins ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Protein Expression ◽  
Treatment Response ◽  
Advanced Ovarian Cancer ◽  
Heat Shock Protein 60 ◽  
Serous Ovarian Cancer ◽  
The Impact ◽  
Hsp60 Protein

ObjectiveHeat shock protein 60 (HSP60) plays an essential role in malignant cell survival. We evaluated the prognostic and treatment predictive value of HSP60 in advanced ovarian cancer.MethodsFresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 fulfilled the eligibility criteria, that is, International Federation of Gynecology and Obstetrics stage IIC-IV, serous/endometrioid tumors, platinum-based chemotherapy, and specimens with 50% tumor cells or greater. Heat shock protein 60 mRNA and protein expression was determined by real-time polymerase chain reaction and immunohistochemistry. We estimated the association between HSP60 and overall survival (OS) and platinum-free interval (PFI) by Cox proportional hazards models and its relationship with treatment response by Fisher’s exact test. Median follow-up was 60 months.ResultsHigh HSP60 mRNA expression was associated with shorter OS (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.3–8.5) and PFI (HR, 3.3; 95% CI, 1.5–7.2). Likewise, high HSP60 protein expression was associated with shorter OS (HR, 3.2; 95% CI, 1.5–7.1) and PFI (HR, 2.6; 95% CI, 1.3–5.3). Median survival for patients with high HSP60 protein expression was 31 months compared with 55 months for low expression cases (P = 0.016). The impact on OS and PFI was even stronger in the subgroup of grade 3 serous tumors. All patients with low HSP60 levels responded to first-line chemotherapy.ConclusionHeat shock protein 60 may identify groups of advanced serous ovarian cancer with different prognosis and treatment response.

Protective Effect of Lycopene on Oxidative Stress-Induced Cell Death of Pancreatic Acinar Cells

2009 ◽  
Vol 1171 (1) ◽  
pp. 570-575 ◽  
Author(s):  
Jeong Yeon Seo ◽  
Atsushi Masamune ◽  
Tooru Shimosegawa ◽  
Hyeyoung Kim
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Protective Effect ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells

Pioglitazone Protect PC12 Cells Against Oxidative Stress Injury: Involvement of Anti-apoptotic Effect and PPARγ Activation

2021 ◽  
Author(s):  
Yali Li ◽  
Jun Long ◽  
Libo Li ◽  
Lijuan Liu ◽  
Ziyao Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Protein Expression ◽  
Protective Effect ◽  
Pc12 Cells ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Time Dependent ◽  
Dependent Manner ◽  
Stress Injury

Abstract Objectives: Using a PC12 cell model with Hydrogen peroxide, we investigated the neuronal apoptotic gene expression and neuronal apoptosis after oxidative stress damage. We further explored protective effect of pioglitazone and its mechanisms. Methods: Taking H2O2 treated PC12 cells as oxidative stress damaged neuron models, MTT and flow cytometry methods were performed to measure the influence of H2O2 on neuronal apoptosis and the protective effect of pioglitazone. Neuronal apoptosis was detected by TUNEL staining. Real-time PCR and Western blot methods were performed to investigate the expression of PPARγ, Bax, Bcl-2 and Caspase-3. Results: H2O2 can induce the apoptosis of PC12 cells in an dose- and time-dependent manner. And H2O2 (100μmol/L, 24h) can induce the expression of PPARγ mRNA and protein (p<0.01). Pioglitazone significantly up-regulated the protein expression of Bax, caspase-3(p<0.01) and decreased the expression of Bcl-2(p<0.01). Pioglitazone can dose-dependently decrease the apoptotic ratio of H2O2-damaged PC12 cells. 1.0×10-6 mol/L pioglitazone can induce PPARγ mRNA and protein expression. Pioglitazone decreased Bax, caspase-3 protein expression(p<0.01) and increased Bcl-2 protein expression(p<0.01), thus down-regulated the expression ratio of Bax/Bcl-2(p<0.01) and decreased the apoptotic ratio of PC12 cells(p<0.01). GW9662, the antagonist of PPARγ, and PPARγ siRNA can offset the protective effect of pioglitazone on PC12 cells to different degrees(p<0.01). Conclusions: hydrogen peroxide can induce apoptosis of PC12 cells in dose- and time-dependent manner. PPARγ activation by pioglitazone can significantly decreased expression of Bax/Bcl-2 and Caspase-3, thus plays a part in neuron protective effects on H2O2-treated PC12 cells. The antagonist and RNAi of PPARγ can offset protective effect of pioglitazone to different degree, which indicates PPARγ activation exerts protective role in decreasing the apoptosis of PC12 cells.

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