scholarly journals Dietary Inorganic Nitrate Protects Hepatic Ischemia-Reperfusion Injury Through NRF2-Mediated Antioxidative Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Shaorong Li ◽  
Hua Jin ◽  
Guangyong Sun ◽  
Chunmei Zhang ◽  
Jinsong Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Sodium Nitrate ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Hepatic Ischemia ◽  
Inorganic Nitrate ◽  
Hepatic Ischemia Reperfusion

Objectives: Hepatic ischemia-reperfusion injury (HIRI) is of common occurrence during liver surgery and liver transplantation and may cause hepatic impairment, resulting in acute liver dysfunction. Nitrate plays an important physiological regulatory role in the human body. Whether dietary nitrate could prevent HIRI is, however, unknown.Methods: A HIRI mouse model was established in that the blood supply to the median lobe and left lateral lobe was blocked for 60 min through the portal vein and related structures using an atraumatic clip. Sodium nitrate (4 mM) was administrated in advance through drinking water to compare the influence of sodium nitrate and normal water on HIRI.Results: Liver necrosis and injury aggravated after HIRI. The group treated with sodium nitrate showed the lowest activities of plasma aminotransferase and lactate dehydrogenase and improved outcomes in histological investigation and TUNEL assay. Mechanistically, sodium nitrate intake increased plasma and liver nitric oxide levels, upregulated nuclear factor erythroid 2-related factor 2 (NRF2)–related molecules to reduce malondialdehyde level, and increased the activities of antioxidant enzymes to modulate hepatic oxidative stress.Conclusions: Dietary inorganic nitrate could prevent HIRI, possibly by activating the NRF2 pathway and modulating oxidative stress. Our study provides a novel therapeutic compound that could potentially prevent HIRI during liver transplantation or hepatic surgery.

scholarly journals MicroRNA-141-3p Attenuates Oxidative Stress-induced Hepatic Ischemia Reperfusion Injury via Keap1/Nrf2 Pathway

2021 ◽  
Author(s):  
Tingting Li ◽  
Qingsong Chen ◽  
Jiangwen Dai ◽  
Zuotian Huang ◽  
Yunhai Luo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Abstract Hepatic ischemia reperfusion injury (IRI) is a major factor affecting the prognosis of liver transplantation through a series of severe cell death and inflammatory responses. MicroRNA-141-3p (miR-141-3p) has been reported to be associated with hepatic steatosis and other liver diseases. However, the potential role of miR-141-3p in hepatic IRI is currently unknown. In the present study, we found that miR-141-3p levels were negatively correlated with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) in liver transplantation patients. The results demonstrated that miR-141-3p was decreased in mouse liver tissue after hepatic IRI in mice and in hepatocytes after hypoxia/reoxygenation (H/R). Overexpression of miR-141-3p directly decreased Kelch-like ECH-associated protein 1 (Keap1) levels and attenuated cell apoptosis in vivo and in vitro, while inhibition of miR-141-3p facilitated apoptosis. Further experiments revealed that overexpression of miR-141-3p also attenuated oxidative stress-induced damage in hepatocytes under H/R conditions. Taken together, our results indicate that miR-141-3p plays a major role in hepatic IRI through the Keap1 signaling pathway, and the present study suggests that miR-141-3p might have a protective effect on hepatic IRI to some extent.

scholarly journals The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury

2016 ◽  
Vol 38 (4) ◽  
pp. 1631-1642 ◽  
Author(s):  
Zhijie Xu ◽  
Jingui Yu ◽  
Jianbo Wu ◽  
Feng Qi ◽  
Huanliang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Treatment Group ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Ischemia ◽  
Hepatic Ischemia ◽  
Group I ◽  
Hepatic Ischemia Reperfusion

Background: Propofol and sevoflurane are widely used in clinical anesthesia, and both have been reported to exert a protective effect in organ ischemia/reperfusion (IR). This study aims to investigate and compare the effects of propofol and sevoflurane on liver ischemia/reperfusion and the precise molecular mechanism. Methods and Materials: Rats were randomized into four groups: the sham group, I/R group, propofol treatment group (infused with 1% propofol at 500 µg· kg-1· min-1), and sevoflurane treatment group (infused with 3% (2 L/min) sevoflurane). The liver ischemia/reperfusion model was used to evaluate the hepatoprotective effect on ischemic injury. Liver enzyme leakage, liver cytokines and histopathological examination were used to evaluate the extent of hepatic ischemia/reperfusion injury. Oxidative stress was investigated by evaluating the levels of Malondialdehyde(MDA), Superoxide Dismutase(SOD) and NO. The terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) assay and western blot were applied to detect apoptosis in the ischemic liver tissue and its mechanism. Results: Both propofol and sevoflurane attenuated the extent of hepatic ischemia/reperfusion injury which is evident from the hisopathological studies and alterations in liver enzymes such as AST and LDH by inhibiting Nuclear factor kappa B (NFκB) activation and subsequent alterations in inflammatory cytokines interleukin-1(IL-1), interleukin-6(IL-6), tumor necrosis factor-alpha (TNF-a) and increased IL10 release. Propofol exhibited a similar protective effect and a lower IL-1 release, while sevoflurane decreased TNF-a leakage more significantly. Meanwhile, oxidative stress was attenuated by reduced MDA and NO and elevated SOD release. The expression of antiapoptotic protein Bcl-2 and Bcl-xl were enhanced while that of apoptotic protein Bax and Bak were reduced by both propofol and sevoflurane to regulate hepatic apoptosis. In addition, propofol downregulated the phosphorylation of AKT and Bad protein, while sevoflurane downregulated the phosphorylation of p38. In addition, Both the treatments had no effect on the expression of AKT, Bad and p38. Conclusion: Both propofol and sevoflurane can protect the liver from ischemia/reperfusion injury by modulating the inflammatory responses reducing oxidative stress and liver apoptosis.

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