Pro‐inflammatory cytokines/chemokines, TNF‐α, IL‐6 and MCP‐1, as biomarkers for the nephro‐ and pneumoprotective effect of silibinin after hepatic ischemia/reperfusion: confirmation by immunihistochemistry and qRT‐PCR

Author(s):  
Georgios Kyriakopoulos ◽  
Maria Lambropoulou ◽  
Georgia Valsami ◽  
Nikolaos Kostomitsopoulos ◽  
Ourania Konstandi ◽  
...  
PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Ziqi Cheng ◽  
Chuanyong Guo

Hepatic ischemia-reperfusion injury (HIRI) is a common phenomenon in liver transplantation and liver surgery. This article is aimed at clarifying the role of pemafibrate in HIRI through JAK2/STAT3β/PPARα. In the experiment, we divided Balb/c into seven groups, namely, normal control (NC), Sham, PEM (1.0 mg/kg), IRI, IRI + PEM (0.1 mg/kg), IRI + PEM (0.5 mg/kg), and IRI + PEM (1.0 mg/kg). We used biochemical assay, histopathological evaluation, immunohistochemistry, RT-PCR and qRT-PCR, ELISA analysis, and other methods to determine the level of serum AST, ALT, IL-1β, and TNF-α in the liver at three time points (2 h, 8 h, and 24 h) after reperfusion of apoptosis factor, autophagy factor, and the JAK2/STAT3/PPARα content in tissues. Our experiment results showed that the pemafibrate can effectively reduce the level of hepatic IR injury. In addition, pemafibrate has anti-inflammatory, antiapoptotic, and antiautophagy effects, which are mediated by the JAK2/STAT3β/PPARα pathway.


2020 ◽  
Vol 14 (1) ◽  
pp. 88-100
Author(s):  
Fares E.M. Ali ◽  
Heba M. Saad Eldien ◽  
Nashwa A.M. Mostafa ◽  
Abdulrahman H. Almaeen ◽  
Mohamed R.A. Marzouk ◽  
...  

Objective: The present study was conducted to elucidate the underlying molecular mechanism as well as the potential hepatoprotective effects of royal jelly (RJ) against hepatic ischemia/reperfusion (IR) injury. Methods: Rats were assigned into four groups; sham (received vehicle), IR (30 minutes ischemia and 45 minutes reperfusion), sham pretreated with RJ (200 mg/kg P.O.), and IR pretreated with RJ (200 mg/kg P.O.). The experiment has lasted for 28 days. Results: Hepatic IR significantly induced hepatic dysfunctions, as manifested by elevation of serum transaminases, ALP and LDH levels. Moreover, hepatic IR caused a significant up-regulation of P38-MAPK, NF-κB-p65, TNF-α and MDA levels along with marked down-regulation of Nrf-2, HO-1, COX-4, cytoglobin, IκBa, IL-10, GSH, GST and SOD levels. Additionally, marked histopathological changes were observed after hepatic IR injury. On the contrary, pretreatment with RJ significantly improved hepatic functions along with the alleviation of histopathological changes. Moreover, RJ restored oxidant/antioxidant balance as well as hepatic expressions of Nrf-2, HO-1, COX-4, and cytoglobin. Simultaneously, RJ significantly mitigated the inflammatory response by down-regulation of P38-MAPK, NF-κB-p65, TNF-α expression. Conclusion: The present results revealed that RJ has successfully protected the liver against hepatic IR injury through modulation of cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-α signaling pathways.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amr H. ELKady ◽  
Bataa M. Elkafoury ◽  
Dalia A. Saad ◽  
Doaa M. Abd el-Wahed ◽  
Walaa Baher ◽  
...  

Abstract Background Hepatic ischemia reperfusion (IR) injury is considered as a main cause of liver damage and dysfunction. The l-arginine/nitric oxide pathway seems to be relevant during this process of IR. Although acute intense exercise challenges the liver with increased reactive oxygen species (ROS), regular training improves hepatic antioxidant status. Also, oxytocin (Oxy), besides its classical functions, it exhibits a potent antistress, anti-inflammatory, and antioxidant effects. This study was designed to evaluate the hepatic functional and structural changes induced by hepatic IR injury in rats and to probe the effect and potential mechanism of moderate intensity exercise training and/or Oxy, in comparison to a nitric oxide donor, l-arginine, against liver IR-induced damage. Results Compared to the sham-operated control group, the hepatic IR group displayed a significant increase in serum levels of ALT and AST, plasma levels of MDA and TNF-α, and significant decrease in plasma TAC and nitrite levels together with the worsening of liver histological picture. L-Arg, Oxy, moderate intensity exercise, and the combination of both Oxy and moderate intensity exercises ameliorated these deleterious effects that were evident by the significant decrease in serum levels of ALT and AST, significant elevation in TAC and nitrite, and significant decline in lipid peroxidation (MDA) and TNF-α, besides regression of histopathological score regarding hepatocyte necrosis, vacuolization, and nuclear pyknosis. Both the moderate intensity exercise-trained group and Oxy-treated group showed a significant decline in TNF-α and nitrite levels as compared to l-Arg-treated group. The Oxy-treated group showed statistical insignificant changes in serum levels of ALT, AST, and plasma levels of nitrite, MDA, TAC, and TNF-α as compared to moderate intensity exercise-trained group. Conclusion The combination of both moderate intensity exercise and Oxy displayed more pronounced hepatoprotection on comparison with l-Arg which could be attributed to their more prominent antioxidant and anti-inflammatory effects but not due to their NO-enhancing effect.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation


2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Di Liu ◽  
Xin Jin ◽  
Chunqi Zhang ◽  
You Shang

Purpose: This article aimed to study the role of sevoflurane pre-conditioning in hepatic ischemia–reperfusion and its potential mechanism. Methods: Rat liver ischemia–reperfusion model was constructed. Serum TNF-α, IL-1β, IL-10, and IL-6 concentrations were detected by ELISA. Malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in liver homogenate were determined. Hematoxylin–Eosin (HE) staining, Tunel, and immunohistochemistry were performed. Ischemia–reperfusion hepatocyte model was established. Cells transfection was conducted. Apoptosis was observed by flow cytometry. Quantitative real-time PCR (qRT-PCR) and Western blotting analysis were used. Results: Compared with I/R group, liver damage degree, liver cell apoptosis, and glucose regulatory protein 78 (Grp78) expression was obviously reduced in rats of SEV group. TNF-α, IL-1β, and IL-6 concentrations were also significantly increased (P<0.01). MDA and NO concentrations were dramatically lower (P<0.01) and SOD concentration was significantly higher (P<0.01). Apoptosis rate, Grp78, PERK, eIF2α, and p-c-JNK/JNK expression was also significantly decreased (P<0.01). Sevoflurane significantly reduced apoptosis and expression of PERK, eIF2α, p-c-JNK/JNK by inhibiting the expression of Grp78 (P<0.01). Conclusion: Sevoflurane relieves hepatic ischemia–reperfusion injury by inhibiting the expression of Grp78.


Author(s):  
Lai Wei ◽  
Yinyin Su ◽  
Siyou Tan ◽  
Yi Zou ◽  
Yixun Tang ◽  
...  

The current study set out to investigate the molecular mechanism of electroacupuncture (EA) stimulation at Yanglingquan acupoint (GB34) in hepatic ischemia-reperfusion injury (HIRI) in rats via regulation of the endothelin-1 (ET-1) mediated transforming growth factor-β-activated kinase-1 (TAK1)-c-Jun NH2-terminal kinase (JNK)/p38 signaling pathway. First, EA stimulation was applied to the constructed rat model of HIRI at GB34. Subsequently, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and myeloperoxidase (MPO) in liver tissues were measured. Apoptotic changes in liver tissues in rats with HIRI were observed using TUNEL staining. Western blot assay was employed to determine the expression patterns of Bcl-2, Bax, c-caspase-3 and the activation of TAK1-JNK/p38 signaling pathway, and immunohistochemistry was conducted to determine the protein expression patterns of c-caspase-3 and ET-1. In addition, ELISA was performed to determine the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in serum. The results demonstrated a significant decline in the activities of AST and ALT and hepatocyte apoptosis in rats with HIRI following EA stimulation. Meanwhile, EA stimulation brought about decreases in the expression levels of Bcl-2, Bax and c-caspase-3, MPO activity, TNF-α, IL-1β and IL-6 in serum, and diminished those of ET-1 in liver tissues, in addition to inhibiting the TAK1-JNK/p38 signaling pathway. Over-expression of ET-1 could counter the inhibitory effects of EA stimulation of HIRI in rats. Together, our findings indicate that EA stimulation at GB34 down-regulates the expression of ET-1, which inhibits the TAK1-JNK/p38 signaling pathway, consequently alleviating HIRI in rats.


Shock ◽  
2000 ◽  
Vol 13 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Peitan Liu ◽  
Baohuan Xu ◽  
Eric Spokas ◽  
Pi-Shiang Lai ◽  
Patrick Y-K Wong

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