Isoliquiritigenin alleviates LPS/ D-GalN-induced acute liver failure by activating the PGC-1α/ Nrf2 pathway to reduce oxidative stress and inflammatory response

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

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Atractylodin ameliorates lipopolysaccharide and d-galactosamine-induced acute liver failure via the suppression of inflammation and oxidative stress

International Immunopharmacology ◽

10.1016/j.intimp.2019.04.005 ◽

2019 ◽

Vol 72 ◽

pp. 348-357 ◽

Cited By ~ 6

Author(s):

Zheng Lyu ◽

Xufeng Ji ◽

Geng Chen ◽

Beiying An

Keyword(s):

Oxidative Stress ◽

Liver Failure ◽

Acute Liver Failure ◽

And Oxidative Stress

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Neuroprotective effect of licochalcone A against oxygen‐glucose deprivation/reperfusion in rat primary cortical neurons by attenuating oxidative stress injury and inflammatory response via the SIRT1/Nrf2 pathway

Journal of Cellular Biochemistry ◽

10.1002/jcb.26477 ◽

2017 ◽

Vol 119 (4) ◽

pp. 3210-3219 ◽

Cited By ~ 16

Author(s):

Xiaohong Liu ◽

Ying Ma ◽

Xiaodi Wei ◽

Ting Fan

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Cortical Neurons ◽

Neuroprotective Effect ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Stress Injury ◽

Primary Cortical Neurons ◽

Nrf2 Pathway ◽

Licochalcone A

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Role of mitophagy regulation by ROS in hepatic stellate cells during acute liver failure

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00032.2018 ◽

2018 ◽

Vol 315 (3) ◽

pp. G374-G384 ◽

Cited By ~ 9

Author(s):

Zhen Tian ◽

Yi Chen ◽

Naijuan Yao ◽

Chunhua Hu ◽

Yuchao Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Superoxide Dismutase ◽

Liver Failure ◽

Acute Liver Failure ◽

Hepatic Stellate Cells ◽

Stellate Cells ◽

Oxygen Species ◽

End Stage Liver Disease ◽

End Stage

Liver sinusoids serve as the first line of defense against extrahepatic stimuli from the intestinal tract. Hepatic stellate cells (HSCs) are pericytes residing in the perisinusoidal space that integrate cytokine-mediated inflammatory responses in the sinusoids and relay these signals to the liver parenchyma. Oxidative stress has been shown to promote inflammation during acute liver failure (ALF). Whether and how oxidative stress is involved in HSC inflammation during ALF remains unclear. Level of systemic oxidative stress is reflected by superoxide dismutase (SOD). Thus, ALF patients were recruited to investigate the correlation between plasma SOD levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from ALF patients who had undergone liver transplantation. SOD2 expression and HSCs activation were investigated by immunohistochemistry. Inflammation, mitophagy, and apoptosis were investigated by immunoblot analysis and flow cytometry in HSCs treated with lipopolysaccharide (LPS) and reactive oxygen species (ROS) donors. The plasma SOD level was significantly increased in patients with ALF compared with those with cirrhosis (444.4 ± 23.58 vs. 170.07 ± 3.52 U/ml, P < 0.01) and was positively correlated with the Model for End-Stage Liver Disease-Na score ( R2 = 0.4720, P < 0.01). In vivo observations revealed that SOD2 immunostaining was increased in ALF patients and mice models, and in vitro experiments demonstrated that LPS/ROS promoted inflammation via inhibiting mitophagy. Moreover, the regulation of inflammation was apoptosis independent in HSCs. LPS-induced increases in oxidative stress promote inflammation through inhibiting mitophagy in HSCs during the process of ALF, providing a novel strategy for the treatment of patients with ALF. NEW & NOTEWORTHY Here we demonstrate that the serum superoxide dismutase (SOD) level is significantly increased in patients with acute liver failure (ALF), and, correlated with the Model for End-Stage Liver Disease-Na score, SOD level dropped in the remission stage of ALF. We identify that, in liver tissue from ALF patients and mice models, manganese-dependent SOD was overexpressed, and show lipopolysaccharide/H2O2 inhibits mitophagy via reactive oxygen species in hepatic stellate cells (HSCs). We show that inhibited mitophagy promotes inflammation in HSCs, whereas mitophagy inducer rescues HSCs from lipopolysaccharide-induced inflammation.

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Pterostilbene Protects Against Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure by Upregulating the Nrf2 Pathway and Inhibiting NF-κB, MAPK, and NLRP3 Inflammasome Activation

Journal of Medicinal Food ◽

10.1089/jmf.2019.4647 ◽

2020 ◽

Vol 23 (9) ◽

pp. 952-960

Author(s):

Erli Zhang ◽

Jingbo Huang ◽

Kun Wang ◽

Qinlei Yu ◽

Chao Zhu ◽

...

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Nlrp3 Inflammasome ◽

Inflammasome Activation ◽

Nrf2 Pathway ◽

Nlrp3 Inflammasome Activation

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Salvianolic Acid C against Acetaminophen-Induced Acute Liver Injury by Attenuating Inflammation, Oxidative Stress, and Apoptosis through Inhibition of the Keap1/Nrf2/HO-1 Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/9056845 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

Chien-Ta Wu ◽

Jeng-Shyan Deng ◽

Wen-Chin Huang ◽

Po-Chou Shieh ◽

Mei-Ing Chung ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Heme Oxygenase 1 ◽

Molecular Evidence ◽

Related Factor ◽

Drug Induced ◽

Mitochondrial Oxidative Stress ◽

Salvianolic Acid

Acetaminophen (APAP) overdose is one of the most common causes of drug-induced acute liver failure in humans. To investigate the hepatoprotective effect of salvianolic acid C (SAC) on APAP-induced hepatic damage, SAC was administered by daily intraperitoneal (i.p.) injection for 6 days before the APAP administration in mice. SAC prevented the elevation of serum biochemical parameters and lipid profile including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), and triacylglycerol (TG) against acute liver failure. Additionally, SAC reduced the content of malondialdehyde (MDA), the cytochrome P450 2E1 (CYP2E1), and the histopathological alterations and inhibited the production of proinflammatory cytokines in APAP-induced hepatotoxicity. Importantly, SAC effectively diminished APAP-induced liver injury by inhibiting nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR4), and mitogen-activated protein kinases (MAPKs) activation signaling pathway. Moreover, SAC enhanced the levels of hepatic activities of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in APAP-induced mice. SAC mainly inhibited the activation of apoptotic pathways by reduction of cytochrome c, Bax, and caspase-3 protein expression. Taken together, we provide the molecular evidence that SAC protected the hepatocytes from APAP-induced damage by mitigating mitochondrial oxidative stress, inflammatory response, and caspase-mediated antiapoptotic effect through inhibition of the Keap1/Nrf2/HO-1 signaling axis.

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