scholarly journals Dexmedetomidine attenuates lipopolysaccharide-induced acute liver injury in rats by inhibiting caveolin-1 downstream signaling pathway

2021 ◽  
Vol 41 (3) ◽  
Author(s):  
Fei Tong ◽  
Wenchao Shen ◽  
Pengtao Song ◽  
Jiafeng Song ◽  
Yonghe Hu ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Liver Tissue ◽  
Acute Liver Injury ◽  
Male Rats ◽  
Tissue Homogenate ◽  
Caveolin 1 ◽  
Significant Difference ◽  
Group D

Abstract Objective: The aim of the present study is to investigate the anti-injury and anti-inflammatory effects of dexmedetomidine (Dex) in acute liver injury induced by lipopolysaccharide (LPS) in Sprague–Dawley rats and its possible mechanism. Methods: The acute liver injury model of male rats was established by injecting LPS into tail vein. The mean arterial pressure (MAP) of rats was recorded at 0–7 h, and lactic acid was detected at different time points. Wet/dry weight ratio (W/D) was calculated. Pathological changes of rat liver were observed by HE staining. ALT and AST levels in serum were detected. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) in liver tissue homogenate and the levels of IL-1β and IL-18 in serum were detected by ELISA. Protein levels of Caveolin-1 (Cav-1), TLR-4 and NLRP3 in liver tissue were tested by immunohistochemistry method. The expression of Cav-1, TLR-4 and NLRP3 mRNA in liver tissue was detected by quantitative polymerase chain reaction (qPCR) to explore its related mechanism. Results: Compared with NS group, serum lactic acid, W/D of liver tissue, MPO, SOD, IL-1β and IL-18 were significantly increased and MAP decreased significantly in LPS group and D+L group. However, compared with NS group, D group showed no significant difference in various indicators. Compared with LPS group, MPO, SOD, IL-1β and IL-18 were significantly decreased and MAP was significantly increased in D+L group. D+L group could significantly increase the level of Cav-1 protein and decrease the level of TLR-4 and NLRP3 protein in liver tissue caused by sepsis. The expression of Cav-1 mRNA was significantly up-regulated and the expression of TLR-4 and NLRP3 mRNA was inhibited in D+L group. Conclusion: Dex pretreatment protects against LPS-induced actue liver injury via inhibiting the activation of the NLRP3 signaling pathway by up-regulating the expression of Cav-1 by sepsis.

Mass Spectrometry-based Label-free Quantitative Proteomic Analysis of CCl4-induced Acute Liver Injury in Mice Intervened by Total Glycosides from Ligustri Lucidi Fructus

2020 ◽  
Vol 17 ◽  
Author(s):  
Qian Lu ◽  
Hai-Zhu Xing ◽  
Nian-Yun Yang
Keyword(s):  
Insulin Resistance ◽  
Liver Injury ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Proteomic Analysis ◽  
Acute Liver Injury ◽  
Liver Cells ◽  
Differentially Expressed ◽  
Liver Protein ◽  
Differentially Expressed Proteins

Background: CCl4 acute liver injury (ALI) is a classical model for experimental research. However, there are few reports involved in the fundamental research of CCl4-induced ALI Ligustri Lucidi Fructus (LLF) are and its prescription have been used to treat hepatitis illness clinically. LLF and its active ingredients displayed anti-hepatitis effects, but the mechanism of function has not been fully clarified Objective: To investigate the proteomic analysis of CCl4-induced ALI, and examine the effects of active total glycosides (TG) from LLF on ALI of mice4, including histopathological survey and proteomic changes of liver tissues, and delineate the possible underlying mechanism. Methods: CCl4 was used to produce ALI mice model. The model mice were intragastrically administrated with TG and the liver his-topathological changes of mice were examined. At the end of test, mice liver samples were collected, after protein denaturation, re-duction, desalination and enzymatic hydrolysis, identification was carried out by nano LC-ESI-OrbiTrap MS/MS technology. The data was processed by Maxquant software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed based on GO and KEGG analysis. Key protein expression was validated by Western blot analysis Results: A total of 705 differentially-expressed proteins were identified during the normal, model and administration group. 9 signifi-cant differential proteins were focused based on analysis. Liver protein expression changes of CCl4-induced ALI mice were mainly involved in several important signal channels, namely FoxO signaling pathway, autophagy-animal, insulin signaling pathway. TG has anti-liver damnification effect in ALI mice, the mechanism of which is related to FoxO1 and autophagy pathways Conclusion: CCl4 inhibited expression of insulin-Like growth factor 1 (Igf1) and 3-phosphoinositide-dependent protein kinase 1 (Pdpk1) in liver cells and induced insulin resistance, thus interfered with mitochondrial autophagy and regeneration of liver cells and the metabolism of glucose and lipid, and caused hepatic necrosis in mice. TG resisted liver injury in mice. TG adjusted the expression level of key proteins Igf1 and Pdpk1 after liver injury and improved insulin resistance, thus promoted autophagy and resisted the liver damage

scholarly journals CD36 deficiency ameliorates drug-induced acute liver injury in mice

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Chen Zhang ◽  
Xiao Shi ◽  
Zhongping Su ◽  
Chao Hu ◽  
Xianmin Mu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Western Blot ◽  
Kinase Inhibitor ◽  
Inflammatory Responses ◽  
Acute Liver Injury ◽  
Protein Adducts ◽  
Sterile Inflammation ◽  
Inflammatory Factor ◽  
Cd36 Deficiency ◽  
Significant Difference

Abstract Background Acetaminophen (APAP) overdose causes hepatotoxicity and even acute liver failure. Recent studies indicate that sterile inflammation and innate immune cells may play important roles in damage-induced hepatocytes regeneration and liver repair. The scavenger receptor CD36 has its crucial functions in sterile inflammation. However, the roles of CD36 in APAP induced acute liver injury remain unclear and warrant further investigation. Methods WT C57BL/6 J and CD36−/− mice were intraperitoneally injected with APAP (300 mg/kg) after fasting for 16 h. Liver injury was evaluated by serum alanine aminotransferase (ALT) level and liver tissue hematoxylin and eosin (H&E) staining. Liver inflammatory factor expression was determined by real-time polymerase chain reaction (PCR). The protein adducts forming from the metabolite of APAP and the metabolism enzyme cytochrome P450 2E1 (CYP2E1) levels were measured by Western blot. Liver infiltrating macrophages and neutrophils were characterized by flow cytometry. RNA sequencing and Western blot were used to evaluate the effect of damage-associated molecular patterns (DAMP) molecule high mobility group B1 (HMGB1) on WT and CD36−/− macrophages. Moreover, PP2, a Src kinase inhibitor, blocking CD36 signaling, was applied in APAP model. Results The expression of CD36 was increased in the liver of mice after APAP treatment. Compared with WT mice, APAP treated CD36−/− mice show less liver injury. There was no significant difference in APAP protein adducts and CYP2E1 expression between these two strains. However, reduced pro-inflammatory factor mRNA expression and serum IL-1β level were observed in APAP treated CD36−/− mice as well as infiltrating macrophages and neutrophils. Moreover, CD36 deficiency impaired the activation of c-Jun N-terminal kinase (JNK) caused by APAP. Interestingly, the lack of CD36 reduced the activation of extracellular regulated protein kinases (Erk) and v-akt murine thymoma viral oncogene homolog (Akt) induced by HMGB1. RNA transcription sequencing data indicated that HMGB1 has a different effect on WT and CD36−/− macrophages. Furthermore, treatment with PP2 attenuated APAP induced mouse liver injury. Conclusion Our data demonstrated that CD36 deficiency ameliorated APAP-induced acute liver injury and inflammatory responses by decreasing JNK activation. CD36 might serve as a new target to reduce acute liver injury.

scholarly journals Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Weitao Ji ◽  
Hongyun Shi ◽  
Hailin Shen ◽  
Jing Kong ◽  
Jiayi Song ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Klf4 Expression ◽  
Mrna And Protein Expression

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

scholarly journals Hepatoprotective Effect of Melatonin in Toxic Liver Injury in Rats

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 304 ◽  
Author(s):  
Oleshchuk ◽  
Ivankiv ◽  
Falfushynska ◽  
Mudra ◽  
Lisnychuk
Keyword(s):  
Liver Injury ◽  
Hepatoprotective Effect ◽  
Male Rats ◽  
Saline Control ◽  
Control Group ◽  
Radical Scavenger ◽  
Thiobarbituric Acid Reactive Substance ◽  
Lipid Hydroperoxides ◽  
Significant Difference ◽  
Toxic Liver Injury

Background and objectives: toxic liver injury results in nitrooxidative stress. Melatonin is a potent free radical scavenger, an inducible nitric oxide synthase (iNOS) inhibitor and an activator of antioxidant enzymes. The aim of this study was to investigate the hepatoprotective effect of exogenous melatonin on animals with acute toxic hepatitis. Material and methods: 36 healthy Sprague-Dawley male rats were split into three equal groups and given carbon tetrachloride (CCl4), 2 g/kg (CCl4 group) or the same dose of CCl4 and melatonin, 10 mg/kg (CCl4/melatonin group) or saline (control group). The effect of melatonin on prooxidant and antioxidant system indexes, NO and NOS levels in serum and liver, data of mitochondrial chain functions and cytolysis in liver were evaluated in all three groups. Results: melatonin significantly decreased activities of AST, ALT, ceruloplasmine and thiobarbituric acid reactive substance (TBARS) in serum. Catalase activity was lowered in serum but not in the liver. Hepatic TBARS, lipid hydroperoxides and glutathione concentrations were decreased, while superoxide dismutase, mitochondrial cytochrome oxidase and succinate dehydrogenase activities increased. Melatonin inhibited synthesis of stable NO metabolites in serum: NO2-by 37.9%; NO3-by 29.2%. There was no significant difference in content NO2-in the liver, but concentration of NO3-increased by 32.6%. Melatonin significantly reduced iNOS concentrations both in serum (59.7%) and liver (57.8%) but did not affect endothelial isoform enzyme activities neither in serum, nor in liver. The histopathological liver lesions observed in the CCl4/melatonin group were less severe than those seen in the CCl4 group. Conclusions: we demonstrated an ameliorating effect of melatonin on prooxidants and antioxidants, NO-NOS systems balance, mitochondrial function and histopathological lesions in the liver in rats with CCl4-induced hepatitis.

The Effectiveness of Tsu-San-Li (St-36) and Tai-Chung (Li-3) Acupoints for Treatment of Acute Liver Damage in Rats

2001 ◽  
Vol 29 (02) ◽  
pp. 221-226 ◽  
Author(s):  
Hsu-Jan Liu ◽  
Sheng-Feng Hsu ◽  
Chang-Chi Hsieh ◽  
Tin-Yun Ho ◽  
Ching-Liang Hsieh ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Acupuncture Therapy ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Male Rats ◽  
Acute Liver Damage ◽  
Glutamate Pyruvate Transaminase ◽  
Serum Glutamate Pyruvate Transaminase ◽  
Glutamate Pyruvate ◽  
Serum Glutamate

This study investigated the effects of acupuncture on carbon tetrachloride (CCl4) induced acute liver injury in male rats (n = 36). The experimental groups were injected with CCl4 before, during, or after acupuncture therapy. Acupoints similar to the human Tsu-San-Li (St-36) and Tai-Chung (Li-3) were needled bilaterally. Rats treated with CCl4 had higher levels of serum glutamate-oxalate-transaminase (sGOT) and serum glutamate-pyruvate-transaminase (sGPT). Comparing the experimental groups, biochemical and pathological parameters of liver injury were significantly reduced when rats were acupunctured after, not before, CCl4-induced hepatotoxicity. Acupuncture at the Tsu-Sa-Li and Tai-Chung acupoints cannot prevent acute liver injury but may be effective in treating liver injury induced by carbon tetrachloride in rats.

Protective effect of dioscin against thioacetamide-induced acute liver injury via FXR/AMPK signaling pathway in vivo

2018 ◽  
Vol 97 ◽  
pp. 481-488 ◽  
Author(s):  
Lingli Zheng ◽  
Lianhong Yin ◽  
Lina Xu ◽  
Yan Qi ◽  
Hua Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Ampk Signaling

scholarly journals Deletion of caveolin-1 attenuates LPS/GalN-induced acute liver injury in mice

2018 ◽  
Vol 22 (11) ◽  
pp. 5573-5582 ◽  
Author(s):  
Tsung-Huang Tsai ◽  
Kabik Tam ◽  
Shu-Fen Chen ◽  
Jun-Yang Liou ◽  
Yi-Chen Tsai ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Caveolin 1
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