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.

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 Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury through inhibiting alveolar macrophages pyroptosis via Keap1/Nrf2/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 (Nrf2 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 and 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. The products of oxidative Stress (ROS, MDA, 15-F2t-Isoprostane) and the antioxidant enzymes (SOD, GSH-PX, CAT) were detected.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 and 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/Nrf2/HO-1 pathway in LIRI. Furthermore, inhibiting Keap1/Nrf2/HO-1 pathway through brusatol administration could aggravate lung tissue damage and inflammatory response after lung I/R. And these effects by brusatol administration could be alleviated by rHMGB1 preconditioning in LIRI .Conclusions : rHMGB1 preconditioning protects against LIRI through suppressing AMs pyroptosis. The molecular mechanism could be partially explained by inhibiting oxidative stress and improving the activity of antioxidative enzymes via Keap1/Nrf2/HO-1 pathway upon rHMGB1 preconditioning.

Sign in / Sign up

Export Citation Format

Share Document