scholarly journals Maresin 1 Ameliorates Lung Ischemia/Reperfusion Injury by Suppressing Oxidative Stress via Activation of the Nrf-2-Mediated HO-1 Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Quanchao Sun ◽  
You Wu ◽  
Feng Zhao ◽  
Jianjun Wang
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Lung Tissue ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Lung Injury Score ◽  
Maresin 1 ◽  
The Impact

Lung ischemia/reperfusion (I/R) injury occurs in various clinical conditions and heavily damaged lung function. Oxidative stress reaction and antioxidant enzymes play a pivotal role in the etiopathogenesis of lung I/R injury. In the current study, we investigated the impact of Maresin 1 on lung I/R injury and explored the possible mechanism involved in this process. MaR 1 ameliorated I/R-induced lung injury score, wet/dry weight ratio, myeloperoxidase, tumor necrosis factor, bronchoalveolar lavage fluid (BALF) leukocyte count, BALF neutrophil ratio, and pulmonary permeability index levels in lung tissue. MaR 1 significantly reduced ROS, methane dicarboxylic aldehyde, and 15-F2t-isoprostane generation and restored antioxidative enzyme (superoxide dismutase, glutathione peroxidase, and catalase) activities. Administration of MaR 1 improved the expression of nuclear Nrf-2 and cytosolic HO-1 in I/R-treated lung tissue. Furthermore, we also found that the protective effects of MaR 1 on lung tissue injury and oxidative stress were reversed by HO-1 activity inhibitor, Znpp-IX. Nrf-2 transcription factor inhibitor, brusatol, significantly decreased MaR 1-induced nuclear Nrf-2 and cytosolic HO-1 expression. In conclusion, these results indicate that MaR 1 protects against lung I/R injury through suppressing oxidative stress. The mechanism is partially explained by activation of the Nrf-2-mediated HO-1 signaling pathway.

scholarly journals Maresin 1 protects the liver against ischemia/reperfusion injury via the ALXR/Akt signaling pathway

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Da Tang ◽  
Guang Fu ◽  
Wenbo Li ◽  
Ping Sun ◽  
Patricia A. Loughran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Serum Aminotransferase ◽  
Primary Mouse ◽  
Maresin 1

Abstract Background Hepatic ischemia/reperfusion (I/R) injury can be a major complication following liver surgery contributing to post-operative liver dysfunction. Maresin 1 (MaR1), a pro-resolving lipid mediator, has been shown to suppress I/R injury. However, the mechanisms that account for the protective effects of MaR1 in I/R injury remain unknown. Methods WT (C57BL/6J) mice were subjected to partial hepatic warm ischemia for 60mins followed by reperfusion. Mice were treated with MaR1 (5-20 ng/mouse), Boc2 (Lipoxin A4 receptor antagonist), LY294002 (Akt inhibitor) or corresponding controls just prior to liver I/R or at the beginning of reperfusion. Blood and liver samples were collected at 6 h post-reperfusion. Serum aminotransferase, histopathologic changes, inflammatory cytokines, and oxidative stress were analyzed to evaluate liver injury. Signaling pathways were also investigated in vitro using primary mouse hepatocyte (HC) cultures to identify underlying mechanisms for MaR1 in liver I/R injury. Results MaR1 treatment significantly reduced ALT and AST levels, diminished necrotic areas, suppressed inflammatory responses, attenuated oxidative stress and decreased hepatocyte apoptosis in liver after I/R. Akt signaling was significantly increased in the MaR1-treated liver I/R group compared with controls. The protective effect of MaR1 was abrogated by pretreatment with Boc2, which together with MaR1-induced Akt activation. MaR1-mediated liver protection was reversed by inhibition of Akt. Conclusions MaR1 protects the liver against hepatic I/R injury via an ALXR/Akt signaling pathway. MaR1 may represent a novel therapeutic agent to mitigate the detrimental effects of I/R-induced liver injury.

scholarly journals Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury through inhibiting alveolar macrophages pyroptosis via Keap1/Nrf-2/HO-1 signal pathway

2020 ◽  
Author(s):  
Lin Fei ◽  
Xiao Jingyuan ◽  
Liang Fangte ◽  
Dai Huijun ◽  
Ye Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Lung Injury ◽  
Reperfusion Injury ◽  
Lung Tissue ◽  
Alveolar Macrophages ◽  
Tissue Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lung Tissue Damage

Abstract Background Lung ischemia-reperfusion injury (LIRI) is a common and complex pathophysiological process that can lead to poor patient outcomes. Inflammasome-dependent macrophage pyroptosis contributes to organ damage caused by ischemia-reperfusion (I/R). Oxidative stress reaction and antioxidant enzymes also play an important role in LIRI. This experiment was conducted to investigate whether preconditioning with rHMGB1 could ameliorate LIRI and explore the mechanisms of its protective effect in a lung I/R mice model. Methods Adult male mice were anesthetized and the left hilus pulmonis was clamped for 60 min, followed by 120 min of reperfusion. rHMGB1 was performed by intraperitoneal injection at 2 h before anesthesia. Brusatol (Nrf-2 antagonist) was given intraperitoneally every other day for a total of five times before surgery. Measurements of pathohistological lung tissue damage, pulmonary wet/dry (W/D) ratios, inflammatory mediators were performed to assess the extent of lung injury after I/R. Alveolar macrophages (AMs) pyroptosis were evaluated by LDH release, caspase-1 expression in flow cytometry, GSDMD expression in immunofluorescent staining. Measurement of the products of oxidative Stress (ROS, MDA, 15-F2t-Isoprostane) and the antioxidant enzymes (SOD, GSH-PX, CAT) were performed. Results Preconditioning with rHMGB1 significantly ameliorated I/R-induced lung injury through measuring the morphology, wet/dry weight ratio, the expressions of IL-1β, IL-6, NF-κB, HMGB1 in lung tissue. rHMGB1 preconditioning remarkably alleviated AMs pyroptosis induced by lung I/R. rHMGB1 preconditioning significantly reduced oxidative stress and restored the activity of antioxidative enzymes. In addition, rHMGB1 preconditioning mediated the activity of Keap1/Nrf-2/HO-1 pathway in LIRI. Furthermore, inhibiting Keap1/Nrf-2/HO-1 pathway through brusatol administration could aggravate lung tissue damage and inflammatory response after lung I/R. Also, brusatol administration could suppresse the antioxidant and anti-pyroptosis effects of rHMGB1 preconditioning in LIRI. Conclusions rHMGB1 preconditioning protects against LIRI through suppressing AMs pyroptosis. The mechanism is partially explained by inhibiting oxidative stress and improving the activity of antioxidative enzymes via Keap1/Nrf-2/HO-1 pathway.

scholarly journals CYP2J2 and EETs Protect Against Pulmonary Hypertension with Lung Ischemia-Reperfusion Injury In Vivo and In Vitro

2021 ◽  
Author(s):  
Yun Ding ◽  
Pengjie Tu ◽  
Yiyong Chen ◽  
Yangyun Huang ◽  
Xiaojie Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Lung Tissue ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert anti-inflammatory, anti-apoptotic, pro-proliferative, and antioxidant effects on the cardiovascular system. However, the role of CYP2J2 and EETs in pulmonary arterial hypertension (PAH) with lung ischemia-reperfusion injury (LIRI) remains unclear. In the present study, we investigated the effects of CYP2J2 overexpression and exogenous EETs on PAH with LIRI in vitro and in vivo.Methods CYP2J2 gene was transfected into rat lung tissue by recombinant adeno-associated virus (rAAV) to increase the levels of EETs in serum and lung tissue. A rat model of PAH with LIRI was constructed by tail vein injection of monocrotaline (50 mg/kg) for 4 weeks, followed by clamping of the left pulmonary hilum for 1 h and reperfusion for 2 h. In addition, we established a cellular model of human pulmonary artery endothelial cells (HPAECs) with TNF-α combined with hypoxic reoxygenation (anoxia for 8 h and reoxygenation for 16 h) to determine the effect and mechanism of exogenous EETs.Results CYP2J2 overexpression significantly reduced the inflammatory response, oxidative stress and apoptosis associated with lung injury in PAH with LIRI. In addition, exogenous EETs suppressed inflammatory response and reduced intracellular reactive oxygen species (ROS) production and inhibited apoptosis in a tumor necrosis factor alpha (TNF-α) combined hypoxia-reoxygenation model of HPAECs. Our further studies revealed that the anti-inflammatory effects of CYP2J2 overexpression and EETs might be mediated by PPARγ pathway; the anti-apoptotic effects might be mediated by the PI3K/Ak pathway.Conclusions CYP2J2 overexpression and EETs protect against PAH with LIRI via anti-inflammation, anti-oxidative stress and anti-apoptosis, suggesting that increased levels of EETs may be a promising strategy for the prevention and treatment of PAH with LIRI.

scholarly journals Bilobalide protects against ischemia/reperfusion-induced oxidative stress and inflammatory responses via the MAPK/NF-κB pathways in rats

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Li ◽  
Jiliang Jiang ◽  
Liangcheng Tong ◽  
Tingting Gao ◽  
Lei Bai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
Muscle Tissue ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Dry Weight ◽  
Protective Effects

Abstract Background Clinically, skeletal muscle ischemia/reperfusion injury is a life-threatening syndrome that is often caused by skeletal muscle damage and is characterized by oxidative stress and inflammatory responses. Bilobalide has been found to have antioxidative and anti-inflammatory effects. However, it is unclear whether bilobalide can protect skeletal muscle from ischemia/reperfusion injury. Methods The effects of bilobalide on ischemia/reperfusion-injured skeletal muscle were investigated by performing hematoxylin and eosin staining and assessing the wet weight/dry weight ratio of muscle tissue. Then, we measured lipid peroxidation, antioxidant activity and inflammatory cytokine levels. Moreover, Western blotting was conducted to examine the protein levels of MAPK/NF-κB pathway members. Results Bilobalide treatment could protected hind limb skeletal muscle from ischemia/reperfusion injury by alleviating oxidative stress and inflammatory responses via the MAPK/NF-κB pathways. Conclusions Bilobalide may be a promising drug for I/R-injured muscle tissue. However, the specific mechanisms for the protective effects still need further study.

scholarly journals Augmenter of Liver Regeneration Reduces Ischemia Reperfusion Injury by Less Chemokine Expression, Gr-1 Infiltration and Oxidative Stress

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1421 ◽  
Author(s):  
Thomas S. Weiss ◽  
Madeleine Lupke ◽  
Rania Dayoub ◽  
Edward K. Geissler ◽  
Hans J. Schlitt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Regeneration ◽  
Reperfusion Injury ◽  
Tissue Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myeloperoxidase Activity ◽  
Augmenter Of Liver Regeneration ◽  
Primary Mouse ◽  
The Impact

Hepatic ischemia reperfusion injury (IRI) is a major complication in liver resection and transplantation. Here, we analyzed the impact of recombinant human augmenter of liver regeneration (rALR), an anti-oxidative and anti-apoptotic protein, on the deleterious process induced by ischemia reperfusion (IR). Application of rALR reduced tissue damage (necrosis), levels of lipid peroxidation (oxidative stress) and expression of anti-oxidative genes in a mouse IRI model. Damage associated molecule pattern (DAMP) and inflammatory cytokines such as HMGB1 and TNFα, were not affected by rALR. Furthermore, we evaluated infiltration of inflammatory cells into liver tissue after IRI and found no change in CD3 or γδTCR positive cells, or expression of IL17/IFNγ by γδTCR cells. The quantity of Gr-1 positive cells (neutrophils), and therefore, myeloperoxidase activity, was lower in rALR-treated mice. Moreover, we found under hypoxic conditions attenuated ROS levels after ALR treatment in RAW264.7 cells and in primary mouse hepatocytes. Application of rALR also led to reduced expression of chemo-attractants like CXCL1, CXCL2 and CCl2 in hepatocytes. In addition, ALR expression was increased in IR mouse livers after 3 h and in biopsies from human liver transplants with minimal signs of tissue damage. Therefore, ALR attenuates IRI through reduced neutrophil tissue infiltration mediated by lower expression of key hepatic chemokines and reduction of ROS generation.

Mechanism of Tripchlorolide Inhibiting Hedgehog Signaling Pathway to Delay Lung Fibrosis

2020 ◽  
Vol 10 (7) ◽  
pp. 992-998
Author(s):  
Shirui Tan ◽  
Qingrong Li ◽  
Feifei Duan ◽  
Qingqing Yuan ◽  
Gang Deng
Keyword(s):  
Signaling Pathway ◽  
Lung Tissue ◽  
Hedgehog Signaling ◽  
Tissue Injury ◽  
Collagen I ◽  
Lung Fibroblasts ◽  
Lung Injury Score ◽  
Mouse Lung ◽  
Hedgehog Signaling Pathway ◽  
Gli 1

Background: The paper aimed to determine whether Tripchlorolide can exert anti-fibrotic effects by up-regulating Sufu to influence the Hedgehog signaling pathway, and to promote the application of Tripchlorolide in diseases associated with the Hedgehog signaling pathway. Material and Methods: In vivo experiment, bronchoalveolar lavage was performed on the 7th day after intratracheal instillation of bleomycin. The number of inflammatory cells and IL-6 levels were analyzed to observe the anti-inflammatory effect of Tripchlorolide. The lung tissues were obtained on the 14th day. The lung tissue injury was observed, and the expressions of a-SMA, collagen I, TGF-β i, Gli 1 and Sufu were determined. In vitro experiments, mouse lung was transfected with lentivirus to make fibroblasts. The Sufii was overexpressed, the changes in Gli 1 and Gli 2 levels were observed. The effects of the overexpressed Sufti of on the phenotype transformed a-SMA and collagen I levels in TGF-β 1 induced mouse lung fibroblasts were observed. Results: After administration with bleomycin, IL-6 level, total number of cells, neutrophils and macrophages in BALF of the Tripchlorolide group mice were reduced. The lung injury score, the expressions of lung tissue TGF-βl, a-SMA and Collagen I were low. The expression of Sufu was high, while the expression of Gli 1 was low. Compared with the groups in which cells were not transfected with lentivirus, the expression of Sufu in the transfected cells increased, and the expressions of Gli 1 and Gli 2 decreased. After stimulation with TGF-β Sufu decreased. Conclusion: Tripchlorolide can inhibit Hedgehog signaling pathway by up-regulating Sufu to exert an anti-fibrotic effect.

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