scholarly journals Tanshinone IIA Protects against Acute Pancreatitis in Mice by Inhibiting Oxidative Stress via the Nrf2/ROS Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Weiwei Chen ◽  
Chenchen Yuan ◽  
Yingying Lu ◽  
Qingtian Zhu ◽  
Xiaojie Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Mouse Models ◽  
Serum Amylase ◽  
Sodium Taurocholate ◽  
Pancreatic Tissue ◽  
Tanshinone Iia ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Nrf2 Knockout

Background. Danshen (Salvia miltiorrhiza Bunge) and its main active component Tanshinone IIA (TSA) are clinically used in China. However, the effects of TSA on acute pancreatitis (AP) and its potential mechanism have not been investigated. In this study, our objective was to investigate the protective effects of TSA against AP via three classic mouse models. Methods. Mouse models of AP were established by caerulein, sodium taurocholate, and L-arginine, separately. Pancreatic and pulmonary histopathological characteristics and serum amylase and lipase levels were evaluated, and changes in oxidative stress injury and the ultrastructure of acinar cells were observed. The reactive oxygen species (ROS) inhibitor N-Acetylcysteine (NAC) and nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice were applied to clarify the protective mechanism of the drug. Results. In the caerulein-induced AP model, TSA administration reduced serum amylase and lipase levels and ameliorated the histopathological manifestations of AP in pancreatic tissue. Additionally, TSA appreciably decreased ROS release, protected the structures of mitochondria and the endoplasmic reticulum, and increased the protein expression of Nrf2 and heme oxygenase 1 of pancreatic tissue. In addition, the protective effects of TSA against AP were counteracted by blocking the oxidative stress (NAC administration and Nrf2 knockout in mice). Furthermore, we found that TSA protects pancreatic tissue from damage and pancreatitis-associated lung injury in two additional mouse models induced by sodium taurocholate and by L-arginine. Conclusion. Our data confirmed the protective effects of TSA against AP in mice by inhibiting oxidative stress via the Nrf2/ROS pathway.

scholarly journals Isoliquiritigenin Ameliorates Acute Pancreatitis in Mice via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Xinnong Liu ◽  
Qingtian Zhu ◽  
Min Zhang ◽  
Tao Yin ◽  
Rong Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Tissue Injury ◽  
Pancreatic Tissue ◽  
Zinc Protoporphyrin ◽  
Dependent Manner ◽  
Protective Effects ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Flavonoid Monomer

Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.

scholarly journals Naringenin Protects against Acute Pancreatitis in Two Experimental Models in Mice by NLRP3 and Nrf2/HO-1 Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Yong Li ◽  
Yiyuan Pan ◽  
Lin Gao ◽  
Jingzhu Zhang ◽  
Xiaochun Xie ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Pancreatic Tissue ◽  
Experimental Models ◽  
Receptor Protein ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Mild Acute Pancreatitis

Background. Naringenin (Nar) is a type of flavonoid and has been shown to have anti-inflammatory and antioxidative properties. However, the effects of Nar on acute pancreatitis (AP) have not been well studied. In this study, we aimed to investigate the function of Nar in a mouse model of AP. Methods. Mild acute pancreatitis (MAP) was induced by caerulein (Cae), and severe acute pancreatitis (SAP) was induced by L-arginine in mice. Nar was administered intraperitoneally at doses of 25, 50, or 100 mg/kg following MAP induction and at a dose of 100 mg/kg following SAP induction. The serum levels of cytokines, lipase, and amylase were determined, and pancreatic and pulmonary tissues were harvested. Results. The serum levels of amylase, lipase, and cytokines were significantly decreased in both MAP and SAP models after Nar treatment. The malondialdehyde (MDA) levels of the pancreatic tissue was significantly reduced in both MAP and SAP after Nar treatment. In contrast, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), total sulfhydryl (T-SH), and non-proteinsulthydryl (NP-SH) were markedly increased in both MAP and SAP after Nar treatment. The injury in pancreatic and pulmonary tissues was markedly improved as evidenced by the inhibited expression of myeloperoxidase, nod-like receptor protein 3, and interleukin 1 beta as well as the enhanced expression of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 in pancreatic tissues. Conclusions. Nar exerted protective effects on Cae-induced MAP and L-arginine-induced SAP in mice, suggesting that Nar may be a potential therapeutic intervention for AP.

scholarly journals Protective Effects of Taurine Chloramine on Experimentally Induced Colitis: NFκB, STAT3, and Nrf2 as Potential Targets

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 479
Author(s):  
Seong Hoon Kim ◽  
Hye-Won Yum ◽  
Seung Hyeon Kim ◽  
Wonki Kim ◽  
Su-Jung Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Parent Compound ◽  
Oxidative Stress Marker ◽  
Heme Oxygenase 1 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Protective Effects ◽  
Taurine Chloramine ◽  
Proinflammatory Mediators ◽  
Experimentally Induced

Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory mediators, such as chemokines and cytokines in many different types of cells. In the present study, we investigated the protective effects of TauCl on experimentally induced colon inflammation. Oral administration of TauCl protected against mouse colitis caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TauCl administration attenuated apoptosis in the colonic mucosa of TNBS-treated mice. This was accompanied by reduced expression of an oxidative stress marker, 4-hydroxy-2-nonenal and proinflammatory molecules including tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 in mouse colon. TauCl also inhibited activation of NFκB and STAT3, two key transcription factors mediating proinflammatory signaling. Notably, the protective effect of TauCl on oxidative stress and inflammation in the colon of TNBS-treated mice was associated with elevated activation of Nrf2 and upregulation of its target genes encoding heme oxygenase-1, NAD(P)H:quinone oxidoreductase, glutamate cysteine ligase catalytic subunit, and glutathione S-transferase. Taken together, these results suggest that TauCl exerts the protective effect against colitis through upregulation of Nrf2-dependent cytoprotective gene expression while blocking the proinflammatory signaling mediated by NFκB and STAT3.

scholarly journals Methylene blue improves hemodynamic shock but increases lipoperoxidation in severe acute pancreatitis pig model

2008 ◽  
Vol 23 (suppl 1) ◽  
pp. 8-16 ◽  
Author(s):  
Roberto Ferreira Meirelles Jr ◽  
Reginaldo Ceneviva ◽  
Fernanda Viaro ◽  
Caroline Floreoto Baldo ◽  
Paulo Roberto Barbosa Evora
Keyword(s):  
Methylene Blue ◽  
Acute Pancreatitis ◽  
Bolus Dose ◽  
Serum Amylase ◽  
Tissue Perfusion ◽  
Pancreatic Tissue ◽  
Control Group ◽  
Hemodynamic Pattern ◽  
Study Results ◽  
Over Time

PURPOSE: Study hemodynamic pattern and lipoperoxidation during methylene blue (MB) treatment on taurocholate - enterokinase induced acute pancreatitis (AP). METHODS: Thirty pigs were equally divided in control group; MB group; AP group; MB previous AP group; and MB after 90 min of induced AP group. MB was given iv in a bolus dose (2mg.kg-1) followed by maintenance dose (2 mg.kg-1.h-1). Hemodynamic parameters were recorded continuously during 180 min by Swan-Ganz catheter. Blood samples were taken every 60 min to determine arterial and venous nitrate, malondialdehyde (MDA) and amylase. Pancreatic tissue was removed for histopathologic study. RESULTS: In AP group MBP and CO decreased over time 33% (p<0.05) and 52% (p<0.05), respectively. In MB previous induced-AP group, there was 70 minutes delay (p<0.05) to decrease MBP and CO. In MB group arterial and venous nitrite decreased (p<0.05) over time. MB infusion increased (p>0.05) serum MDA when associated to AP. After induced AP, MB did not reverse MBP and CO decrease. There was no difference in serum amylase and necro-hemorrhagic findings with MB treatment. CONCLUSIONS: In this taurocholate-induced AP model MB treatment delayed hemodynamic shock and decreases serum nitrate levels but increases serum MDA levels. No volemic replacement was done and it may have been a mitigated factor to a poor tissue perfusion and impairment microcirculation. Further investigations are needed to elucidate MB treatment role during AP treatment.

scholarly journals High-Fat Diet Aggravates the Intestinal Barrier Injury via TLR4-RIP3 Pathway in a Rat Model of Severe Acute Pancreatitis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Ying-ru Su ◽  
Yu-pu Hong ◽  
Fang-chao Mei ◽  
Chen-yang Wang ◽  
Man Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Severe Acute Pancreatitis ◽  
High Fat Diet ◽  
Sodium Taurocholate ◽  
Intestinal Barrier ◽  
High Body Mass Index ◽  
High Fat ◽  
Junction Protein

Objective. For patients with severe acute pancreatitis (SAP), a high body mass index (BMI) increases the possibility of infection derived from the intestine. In this study, we evaluate whether TAK242 can alleviate severe acute pancreatitis-associated injury of intestinal barrier in high-fat diet-fed rats. Methods. A SAP model was established by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. Thirty Sprague-Dawley (SD) adult rats were randomly divided into five groups: standard rat chow (SRC) normal (SN), SRC SAP (SAP), high-fat diet normal (HN), HFD SAP (HSAP), and TLR4 inhibitor pretreatment HFD SAP (HAPT) groups. Intraperitoneal injection of 3 mg/kg TAK242 was administered 30 minutes before SAP model establishment in the HAPT group. Rats were sacrificed 12 hours after SAP modeling, followed by blood and pancreatic and distal ileum tissue collection for further analyses. Changes in the pathology responses of the rats in each group were assessed. Result. Analyses of serum amylase, lipase, cholesterol, triglyceride, IL-1β, IL-6, DAO, and serum endotoxin as well as tight junction protein expression including zonula occluden-1 and occludin indicated that high-fat diet aggravated SAP-induced intestinal barrier injury via increasing inflammatory response. In addition, the level of necroptosis was significantly higher in the SAP group compared with the SN group while the HSAP group exhibited more necroptosis compared with the SAP group, indicating the important role of necroptosis in pancreatitis-associated gut injury and illustrating that high-fat diet aggravated necroptosis of the ileum. Pretreatment with TLR4 inhibitor significantly alleviated inflammatory response and reduced necroptosis and level of oxidative stress while improving intestinal barrier function. Conclusion. High-fat diet aggravated SAP-induced intestinal barrier injury via inflammatory reactions, necroptosis, and oxidative stress. Inhibition of TLR4 by TAK242 reduced inflammation, alleviated necroptosis, and lowered the level of oxidative stress and then protected the intestinal barrier dysfunction from SAP in high-fat diet-fed rats.

scholarly journals Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 781 ◽  
Author(s):  
Roberta Fusco ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
Tiziana Genovese ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Interleukin 1 ◽  
Antioxidant Properties ◽  
Pancreatic Tissue ◽  
Intercellular Adhesion Molecule ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Intercellular Adhesion Molecule 1 ◽  
Colon Tissue ◽  
Necrosis Factor Alpha

Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.

scholarly journals Gypenosides Prevent H2O2-Induced Retinal Ganglion Cell Apoptosis by Concurrently Suppressing the Neuronal Oxidative Stress and Inflammatory Response

2020 ◽  
Vol 70 (4) ◽  
pp. 618-630 ◽  
Author(s):  
Hong-Kan Zhang ◽  
Yuan Ye ◽  
Kai-Jun Li ◽  
Zhen-ni Zhao ◽  
Jian-Feng He
Keyword(s):  
Oxidative Stress ◽  
Optic Neuritis ◽  
Ganglion Cells ◽  
Nerve Fibers ◽  
Inflammatory Factors ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Retinal Ganglion ◽  
Apoptotic Pathway ◽  
Neuroprotective Effects

AbstractOur previous study demonstrated that gypenosides (Gp) exert protective effects on retinal nerve fibers and axons in a mouse model of experimental autoimmune optic neuritis. However, the therapeutic mechanisms remain unclear. Thus, in this study, a model of oxidative damage in retinal ganglion cells (RGCs) was established to investigate the protective effect of Gp, and its possible influence on oxidative stress in RGCs. Treatment of cells with H2O2 induced RGC injury owing to the generation of intracellular reactive oxygen species (ROS). In addition, the activities of antioxidative enzymes decreased and the expression of inflammatory factors increased, resulting in an increase in cellular apoptosis. Gp helped RGCs to become resistant to oxidation damage by directly reducing the amount of ROS in cells and exerting protective effects against H2O2-induced apoptosis. Treatment with Gp also reduced the generation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased nuclear respiratory factor 2 (Nrf-2) levels so as to increase the levels of heme oxygenase-1 (HO-1) and glutathione peroxidase 1/2 (Gpx1/2), which can enhance antioxidation in RGCs. In conclusion, our data indicate that neuroprotection by Gp involves its antioxidation and anti-inflammation effects. Gp prevents apoptosis through a mitochondrial apoptotic pathway. This finding might provide novel insights into understanding the mechanism of the neuroprotective effects of gypenosides in the treatment of optic neuritis.

scholarly journals Tanshinone IIA Protects against Acute Pancreatitis in Mice by Inhibiting Oxidative Stress via the Nrf2/ROS Pathway

Pancreatology ◽  
2020 ◽  
Vol 20 ◽  
pp. S22-S23
Author(s):  
W. Chen ◽  
C. Yuan ◽  
Q. Zhu ◽  
J. Chen ◽  
D. Deng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Tanshinone Iia

Protective effect of Fragarria ananassa and Vaccinium corymbosum fruit extracts against L-arginine induced acute pancreatitis in rats

2019 ◽  
Author(s):  
Siva Reddy Challa ◽  
Veena Gadicherla ◽  
Mandava V. Basaveswara Rao ◽  
P. Ramakrishna ◽  
K.Pavan Kumar
Keyword(s):  
Acute Pancreatitis ◽  
Protective Effect ◽  
Dna Fragmentation ◽  
Antioxidant Properties ◽  
Vaccinium Corymbosum ◽  
Pancreatic Tissue ◽  
Protective Effects ◽  
Tissue Samples ◽  
Fruit Extracts ◽  
Histopathological Studies

The study was aimed to evaluate the protective effects of alcoholic extracts of Strawberry and Blueberry fruits [AESF and AEBF] in acute pancreatitis in rats. Treatment groups received AESF and AEBF at doses of 200 and 400 mg/kg for 7 days with prior injections of L-arginine on 5th day. Biochemical parameters were estimated in serum and pancreatic tissue samples. Histopathological studies and DNA fragmentation assay were carried out in isolated pancreatic tissue. The results of the study indicated that treatment of AESF and AEBF exhibited a significant dose dependent protective effect. Upon the treatment, anti-oxidant enzymes were significantly (*pless than 0.05) increased. Biochemical results were correlated with the histopathological findings. In addition, the DNA fragmentation assay showed an intact DNA in pancreatic cells of treated groups. In conclusion, berry fruit extracts exerted a potential protective effect against L-arginine induced damage in rat pancreas, at least in part, due to its antioxidant properties.

scholarly journals Effects of tanshinone IIA on fibrosis in a rat model of cirrhosis through heme oxygenase-1, inflammation, oxidative stress and apoptosis

2016 ◽  
Vol 13 (4) ◽  
pp. 3036-3042 ◽  
Author(s):  
MING SHU ◽  
XIAO-RONG HU ◽  
ZUO-AN HUNG ◽  
DAM-DAN HUANG ◽  
SHUN ZHANG
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Rat Model ◽  
Tanshinone Iia ◽  
Heme Oxygenase 1
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