scholarly journals LP-cs Ameliorated CCl 4 -Induced Acute Liver Injury by Suppression of Cellular Stress

2021 ◽  
Author(s):  
Zeping Xu ◽  
Xiaofeng Li ◽  
Yuying Li ◽  
Ping Wang ◽  
Junnan Wu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Lactobacillus Plantarum ◽  
Inflammatory Responses ◽  
Acute Liver Injury ◽  
Regulatory Protein ◽  
High Mobility ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Related Factor

Abstract Background: Acute liver injury (ALI) involves excessive oxidative stress(OS) and inflammatory responses, leading to a high mortality rate due to lack of effective therapy. Carbon tetrachloride (CCl4) is widely used to induce ALI by induction of reactive oxygen species. Probiotics, including Lactobacillus plantarum ST-III, have been shown to produce antibacterial and antioxidant substances such as organic acids or bacteriocins that reduce liver damage. Nevertheless, the effect of Lactobacillus plantarum ST-III culture supernatant (L-P-cs) on CCl4-induced liver injury remains unclear.Methods: Mice were pretreated with L-P-cs or medium for 14days before one dose of 0.2% CCl4 at 10ml/kg body weight delivered by intraperitoneal injection. CCl4-induced liver injury was examined by measuring serum levels of liver transaminases and high mobility-group box 1 protein (HMGB1) and liver histological staining. Inflammation and apoptosis in liver were evaluated by real-time PCR, enzyme-linked immunosorbent assay (ELISA), and TUNEL staining. Apoptosis in NCTC 1469 cells was detected using CCK8 and western blotting (WB). In liver, OS and endoplasmic reticulum stress(ERS)-related proteins were measured using kits and WB.Results: L-P-cs significantly ameliorated CCl4-induced liver injury and reduced CCl4- induced inflammatory response and apoptosis, consistent with NCTC 1469 cells' results. L-P-cs also restored CCl4-induced increases in cell OS and ERS to normalize liver function. Specifically, L-P-cs pretreatment decreased CCl4-induced increases in nuclear factor (erythroid-2 related) factor 2, HO-1, superoxide dismutase, glucose regulatory protein, and activating transcription factor 6.Conclusion: L-P-cs synergistically improves liver lobule necrosis, hepatocyte inflammation, and apoptosis by reducing liver OS and ERS.

scholarly journals Preventive Effect of Lactobacillus Plantarum HFY15 on Oxidative Damage and Acute Liver Injury Induced by Carbon Tetrachloride (CCl 4 ) in Mice

2021 ◽  
Author(s):  
Xingyao Long ◽  
Pan Wang ◽  
Yujing Zhou ◽  
Qiang Wang ◽  
Lixuan Ren ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Oxidative Damage ◽  
Lactobacillus Plantarum ◽  
Acute Liver Injury ◽  
Animal Experiments ◽  
B Cell Lymphoma ◽  
Related Factor ◽  
Preventive Effect ◽  
Antioxidant Genes

Abstract BackgroundCarbon tetrachloride (CCl4) is a widely used hepatic toxin that causes acute liver injury through pathological mechanisms such as oxidative stress, inflammation, and apoptosis. In this experiment, mice were treated with Lactobacillus plantarum (LP) HFY15, silymarin, and Lactobacillus delbruechii subsp. bulgaricus (LDSB) for two weeks, and intraperitoneal injection of CCl4-induced acute liver injury to study the preventive effect of LP-HFY on CCl4-induced acute liver injury, especially in oxidative damage. ResultsThe survival rate of LP-HFY15 in artificial gastric juice is 92.1%, and the growth efficiency in bile salt is 78.8%. Animal experiments show that LP-HFY15 reduces the liver index of mice, reduces the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the content of triglycerides (TG), malondialdehyde (MDA) and reactive oxygen species (ROS) in the serum of mice. LP-HFY15 also increased the antioxidant genes, such as nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase (HO-1), NAD(P)H:quinone oxidoreductase (NQO1), and increases the activity of superoxide dismutation (SOD), catalase (CAT), and glutathione (GSH) in the serum and gene level. At the same time, LP-HFY15 reduced the levels of cytokines IL-6, TNF-α, and IFN-γ in the serum and liver, increased antiapoptosis gene B-cell lymphoma-2 (Bcl-2) expression in the liver of mice, and inhibit the expression of proapoptotic genes Bcl-2-associated X (Bax) and Caspase-3. ConclusionsCompared with LDSB, LP-HFY15 has a greater alleviating effect on the liver injury caused by CCl4. These findings demonstrate that LP-HFY15 has great potential and research value in the future as a food supplement for preventing acute liver damage.

scholarly journals Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling

2020 ◽  
Vol 11 ◽  
Author(s):  
Qiushi Xu ◽  
Yunhui Fan ◽  
Juan J. Loor ◽  
Yusheng Liang ◽  
Xudong Sun ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
High Mobility ◽  
Hepatoprotective Effect ◽  
Receptor Protein ◽  
Related Factor ◽  
Protective Effects ◽  
Toll Like Receptor 4 ◽  
Sequestosome 1 ◽  
Underlying Mechanisms

Cardamonin (CD), a naturally occurring chalcone derived from the Alpinia species, has been shown to exert antioxidant and anti-inflammatory activity, but its role in the prevention of acetaminophen- (APAP-) induced hepatotoxicity remains elusive. The objective of this study was to determine the protective effects of CD against APAP-induced acute liver injury (ALI) and the underlying mechanisms. Wild-type or transcription factor nuclear factor erythroid 2-related factor 2- (NFE2L2-) deficient mice were treated with CD (50 or 100 mg/kg, i.p.) or vehicle for 24 h. Subsequently, these mice were challenged with APAP (400 mg/kg, i.p.) for 6 h. Liver and blood samples were collected to evaluate liver injury and protein abundance. Treatment with CD significantly reduced APAP-induced hepatotoxicity. Furthermore, CD effectively reduced APAP-induced inflammation by inhibiting high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), and NOD-like receptor protein 3 (NLRP3) signaling. In addition, CD induced activation of sequestosome 1 (p62) and NFE2L2 signaling and facilitated autophagy. By applying autophagy inhibitor 3-methyladenine (3-MA; 20 mg/kg, i.p.), further mechanistic exploration revealed that NFE2L2 deficiency promoted autophagic activity induced by CD treatment, which was conducive to the hepatoprotective effect of CD against APAP-induced hepatoxicity in NFE2L2−/− mice. Overall, data suggest that CD has hepatoprotective effect against APAP-induced ALI, which might contribute to the activation of NFE2L2 and autophagy.

scholarly journals Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

2021 ◽  
Vol 11 (1) ◽  
pp. 390
Author(s):  
Beom-Rak Choi ◽  
Il-Je Cho ◽  
Su-Jin Jung ◽  
Jae-Kwang Kim ◽  
Dae-Geon Lee ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Antioxidant Activities ◽  
Body Weight Gain ◽  
Histopathological Analysis ◽  
Related Factor ◽  
Mrna Levels ◽  
Protective Effects ◽  
Lemon Balm

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

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 Serum levels of P-selectin in men with high-functioning autism

2008 ◽  
Vol 193 (4) ◽  
pp. 338-339 ◽  
Author(s):  
Yasuhide Iwata ◽  
Kenji J. Tsuchiya ◽  
Sumiko Mikawa ◽  
Kazuhiko Nakamura ◽  
Yoshifumi Takai ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
High Functioning Autism ◽  
Immune Dysfunction ◽  
Serum Levels ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
High Functioning ◽  
Selectin Family ◽  
Spectrum Disorders

SummaryImmune dysfunction has been proposed as a mechanism for the pathophysiology of autistic-spectrum disorders. The selectin family of adhesion molecules plays a prominent role in immune/inflammatory responses. We determined the serum levels of three types of soluble-form selectin (sP, sL and sE) in 15 men with high-functioning autism and 22 age-matched healthy controls by enzyme-linked immunosorbent assay. Levels of sP-selectin and sL-selectin were significantly lower in patients than in controls. Furthermore, sP-selectin levels were negatively correlated with impaired social development during early childhood.

Angiopoietin-Like Protein 7 and Short-Term Mortality in Acute Heart Failure

2020 ◽  
Vol 10 (2) ◽  
pp. 116-124 ◽  
Author(s):  
Chongyu Zhang ◽  
Xin He ◽  
Jingjing Zhao ◽  
Yalin Cao ◽  
Jian Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Heart Failure ◽  
Inflammatory Responses ◽  
Statistical Significance ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Short Term ◽  
Logistic Regression Models ◽  
Increased Risk ◽  
Short Term Mortality

Introduction: Angiopoietin-like protein 7 (ANGPTL7) is involved in extracellular matrix expression and inflammatory responses. However, the prognostic utility of ANGPTL7 among patients with acute heart failure (AHF) remains unclear. Objective: To evaluate the association between ANGPTL7 and short-term mortality due to AHF. Methods and Results: Patients with AHF were prospectively studied. Serum levels of ANGPTL7 were measured by an enzyme-linked immunosorbent assay. Associations between 30- and 90-day mortality and tertiles of ANGPTL7 were assessed by multivariate logistic regression models. The study comprised 142 patients. Median patient age was 68 years, and 69.7% were male. There were 20 deaths within 30 days and 37 deaths within 90 days. Crude rates of 30-day mortality in low, intermediate, and high tertiles of ANGPTL7 were 4.6, 14.6, and 22.9%, respectively. Crude rates of 90-day mortality of corresponding tertiles were 15.2, 25.0, and 37.5%. After adjusting for potential confounders, including NT-proBNP, the high tertile of ANGPTL7 was associated with a significantly increased risk of both 30-day mortality (odds ratio [OR]: 6.77, 95% confidence interval [CI]: 1.41–32.61, p = 0.017) and 90-day mortality (OR: 3.78, 95% CI: 1.38–10.36, p = 0.010) compared with the low tertile of ANGPTL7. Although mortality risk tended to be higher in the intermediate tertile than the low tertile, it did not reach statistical significance (OR: 3.75, 95% CI: 0.73–19.14, p = 0.113 for 30-day mortality; OR: 1.88, 95% CI: 0.66–5.34, p = 0.236 for 90-day mortality). Conclusions: Serum level of ANGPTL7 was independently associated with short-term mortality among patients with AHF.

Reduced Serum Levels of Cluster of Differentiation 200 in Alcohol-Dependent Patients

2020 ◽  
Vol 55 (4) ◽  
pp. 391-394
Author(s):  
Abhishek Chaturvedi ◽  
Guruprasad Rao ◽  
Samir Kumar Praharaj ◽  
Kanive Parashiva Guruprasad ◽  
Vivek Pais
Keyword(s):  
Alcohol Dependence ◽  
Alcohol Withdrawal ◽  
Addiction Treatment ◽  
Regulatory Protein ◽  
Serum Levels ◽  
Regulatory Proteins ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Cluster Of Differentiation ◽  
Alcohol Dependent

Abstract Aim Chronic alcohol consumption can activate and dysregulate the neuroimmune system which leads to neuroinflammation. Neuroimmune regulatory proteins (NIReg) (e.g. Cluster of Differentiation 200 (CD200)) are the regulators of innate immune response and are responsible for silencing the innate immunity and suppression of inflammation. In this study, we explored the changes of serum levels of CD200 in patients with alcohol dependence at baseline, after one-week alcohol withdrawal and after one-month of alcohol abstinence. Methods Seventeen patients with alcohol dependence admitted for de-addiction treatment and 12 healthy controls were enrolled in the study. Blood samples were collected at baseline, after one-week, and after one-month, and CD200 levels were measured using enzyme-linked immunosorbent assay kit and compared with the healthy controls. Results The serum level of the neuroimmune regulatory protein CD200 in alcohol dependent group (at baseline) was significantly lower compared to healthy controls (p=0.003), and increased after one-week, and one-month period. Conclusion The present study indicates that decrease of CD200 serum levels in alcohol dependent patients and its rise during alcohol withdrawal and abstinence may provide a preliminary evidence of the role of neuroimmune regulatory proteins in neuroadaptation during alcohol withdrawal.

scholarly journals Puerarin mitigates acute liver injury in septic rats by regulating proinflammatory factors and oxidative stress levels

2021 ◽  
Vol 20 (11) ◽  
pp. 2305-2310
Author(s):  
Jinan Zheng ◽  
Qing Huang ◽  
Jingjing Fang
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Serum Levels ◽  
Expression Level ◽  
Sepsis Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Tnf Α ◽  
Proinflammatory Factors

Purpose: To determine the protective effect of puerarin against acute liver injury in septic rats, and the mechanism involved.Methods: Eighty-seven Sprague-Dawley (SD) rats were assigned to control, sepsis and puerarin groups (each having 29 rats). Serum levels of NF-kB, TNF-α, IL-1 β, IL-6, ALT and AST were assayed. Liver lesions and levels of NO, SOD, iNOS and malondialdehyde (MDA) were measured using standard procedures.Results: Compared with the control group, the levels of NF-kB, TNF-α, IL-1β, IL-6, AST, ALT, NO, MDA and iNOS significantly increased in the sepsis group, while SOD level decreased significantly. In contrast, there were marked decreases in NF-kB, TNF-α, IL-1β, AST, ALT, NO, MDA and iNOS in puerarin group, relative to the sepsis group, while SOD expression level was significantly increased (p <0.05). The level of p-p38 in liver of septic rats was up-regulated, relative to control rats, while Nrf2 significantly decreased (p < 0.05). The expression level of p-p38 in the puerarin group was significantly decreased, relative to the sepsis group, while the expression level of Nrf2 significantly increased (p < 0.05).Conclusion: Puerarin mitigates acute liver injury in septic rats by inhibiting NF-kB and p38 signaling pathway, down-regulating proinflammatory factors, and suppressing oxidative stress. Thus, puerarin may be developed for use in the treatment liver injury.

scholarly journals Protective and Therapeutic Effects of Nanoliposomal Quercetin on Acute Liver Injury in Rats

2020 ◽  
Author(s):  
Xiangyan Liu ◽  
Yang Zhang ◽  
Ling Liu ◽  
Yifeng Pan ◽  
Yu Hu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Acute Liver Injury ◽  
Serum Levels ◽  
Spherical Particles ◽  
Therapeutic Effects ◽  
Drug Induced ◽  
Liposomal Nanoparticles ◽  
Quercetin Treatment ◽  
Injured Liver

Abstract Background Quercetin, a pigment (flavonoid) found in many plants and foods, has good effects on protecting liver function but poor solubility and bioavailability in vivo. A drug delivery system can improve the accumulation and bioavailability of quercetin in liver. Objective In this study, we used liposomal nanoparticles to entrap quercetin and evaluated its protective and therapeutic effects on drug-induced liver injury in rats. Design The nanoliposomal quercetin was prepared by a thin film evaporation-high pressure homogenization method and characterized by morphology, particle size and drug content. Acute liver injury was induced in rats by composite factors, including carbon tetrachloride injection, high-fat corn powder intake and ethanol drinking. After pure quercetin or nanoliposomal quercetin treatment, liver function was evaluated by detecting serum levels of glutamic-pyruvic transaminase (GPT), glutamic-oxal acetic transaminase (GOT) and direct bilirubin (DBIL). Histology of injured liver tissues was evaluated by hematoxylin and eosin staining. Results and discussion On histology, liposomal nanoparticles loading quercetin were evenly distributed spherical particles. The nanoliposomal quercetin showed high bioactivity and bioavailability in rat liver and markedly attenuated the liver index and pathologic changes in injured liver tissue. With nanoliposomal quercetin treatment, the serum levels of GPT, GOT and DBIL were significantly better than treated with pure quercetin. Using liposomal nanoparticles to entrap quercetin might be an effective strategy to reduce hepatic injury and protect hepatocytes against damage. Conclusions Liposomal nanoparticles may improve the solubility and bioavailability of quercetin in liver. Furthermore, nanoliposomal quercetin could effectively protect rats against acute liver injury and may be a new hepatoprotective and therapeutic agent for patients with liver diseases.

scholarly journals S100A6 Promotes Inflammation and Infiltration of Mononuclear/Macrophages via the p-P38 and p-JNK Pathways in Acute Liver Injury

2021 ◽  
Author(s):  
He Tong ◽  
Li Wang ◽  
Kefan Zhang ◽  
Jing Shi ◽  
yongshuai Wu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Acute Liver Injury ◽  
S100 Protein ◽  
Inflammatory Cells ◽  
Liver Cells ◽  
Danger Signal ◽  
Tnf Α

Abstract BackgroundThe phagocytic S100 protein, which mediates inflammatory responses and recruits inflammatory cells to sites of tissue damage, has long been known to be expressed in cells of myeloid origin. S100A6 belongs to the A group of the S100 protein family of Ca2+-binding proteins. Currently, the mechanism by which S100A6 mediates the inflammatory response and recruits inflammatory cells to the tissue injury site is unknown.MethodsA mouse model of carbon tetrachloride (CCl4)-induced acute liver injury (ALI) was established, and the transcriptomes of postinjury 2d and 5d liver tissues were sequenced. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) in the supernatant of the liver. Immunohistochemical analysis confirmed the expression of S100A6 in the liver cells. In vitro experiments proved the pro-inflammatory function of S100A6, and western blotting (WB) showed that the pathways were activated. The transwell experiment showed the infiltration of mononuclear/macrophages.ResultsWe found that S100A6 is highly expressed in liver cells during the most severe period of ALI, suggesting that it acts as an endogenous danger signal and has a pro-inflammatory function. In vitro, the mouse S100A6 recombinant protein was used to stimulate liver Kupffer cells to promote the secretion of TNF-α, IL-1β, IL-6, and IL-8. Further mechanistic experiments revealed that S100A6 acts as an endogenous danger signal to activate p-P38 and p-JNK downstream of the TLR4 and P65 pathways. Similarly, transcriptome data showed that S100A6 can activate the inflammatory response in Kuffer cells. WB revealed that S100A6 had no significant effect on cell apoptosis. To continue to explore the mechanism of monocyte/macrophage infiltration, we found that TNF-α stimulates liver cells as the main source of CCL2. TNF-α can initiate the p-P38 and p-JNK pathways of liver cells to produce CCL2, thereby recruiting the infiltration of mononuclear/macrophages. ConclusionsTaken together, S100A6 is an endogenous danger signal that mediates inflammatory responses and recruits inflammatory cells to sites of tissue damage.

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