S-adenosylmethionine deficiency and TNF-α in lipopolysaccharide-induced hepatic injury

1998 ◽  
Vol 275 (1) ◽  
pp. G125-G129 ◽  
Author(s):  
Rajender K. Chawla ◽  
Walter H. Watson ◽  
Charles E. Eastin ◽  
Eun Y. Lee ◽  
Jack Schmidt ◽  
...  
Keyword(s):  
Liver Injury ◽  
De Novo ◽  
Normal Liver ◽  
Fold Increase ◽  
Saline Group ◽  
Saline Control ◽  
Control Group ◽  
Lps Challenge ◽  
Tnf Α ◽  
Factor Α

S-adenosylmethionine (Adomet) is a substrate for de novo synthesis of choline. Adomet deficiency occurs in certain types of liver injury, and the injury is attenuated by exogenous Adomet. Tumor necrosis factor-α (TNF-α) is also a mediator of these models of hepatotoxicity. We investigated the role of Adomet in lipopolysaccharide (LPS)-induced liver injury in rats made deficient in both Adomet and choline. Rats were maintained on either a methionine-restricted and choline-deficient (MCD) diet or a diet containing sufficient amounts of all nutrients [methionine and choline sufficient (MCS)] and then administered either LPS or saline. MCS-LPS rats had normal liver histology and no change in serum transaminases compared with the MCS-saline control group. MCD-saline rats had hepatosteatosis but no necrosis, and a five- to sevenfold increase in transaminases vs. the MCS-saline group. MCD-LPS rats additionally had hepatonecrosis and a 30- to 50-fold increase in transaminases. Exogenous Adomet administration to MCD-LPS rats corrected the hepatic deficiency of Adomet but not of choline, prevented necrosis but not steatosis, and attenuated transaminases. Serum TNF-α was sixfold higher in MCD rats even without LPS challenge and 300-fold higher with LPS challenge. Exogenous Adomet attenuated increased serum TNF-α in MCD-LPS rats.

scholarly journals Oxidative Stress and Neuronal Injury After Cannabis and Ketamine Administration

2021 ◽  
Vol 18 ◽  
pp. 126-135
Author(s):  
Omar M. E. Abdel-Salam ◽  
Eman R. Youness ◽  
Amany Ameen Sleem ◽  
Enayat A. Omara
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Mediators ◽  
Cannabis Sativa ◽  
Paraoxonase 1 ◽  
Saline Control ◽  
Control Group ◽  
Neuronal Necrosis ◽  
Tnf Α ◽  
Markers Of Oxidative Stress ◽  
Factor Α

Cannabis sativa and ketamine are common substances of abuse causing psychotic events and neurodegeneration. In this study, the effect of pretreatment with Cannabis sativa extract on oxidative stress, inflammatory mediators and brain damage induced by ketamine was investigated. Rats were treated with subcutaneous injections of cannabis extract (10, 20, 30 or 40 mg/kg; expressed as Δ9-THC content) daily for three weeks and then in combination with ketamine (15 mg/kg, intraperitoneally) for another 5 days. Rats were tested for biochemical markers of oxidative stress including malondialdehyde (MDA) reduced glutathione (GSH), and nitric oxide (NO) concentrations in brain. Paraoxonase-1 (PON-1) activity, and levels of the proinflammatory cytokines, interleukin-1β (IL-1β), and tumour necrosis factor-α (TNF-α) in brain were also determined at the end of treatment period. Results indicated that compared with the saline control group, ketamine induced significant elevation in brain MDA and NO, which was accompanied by depletion of GSH and inhibition of PON-1 activity. Ketamine also significantly increased brain IL-1β and TNF-α and induced neuronal necrosis, apoptosis and vacuolation. Cannabis sativa (20-40 mg/kg) pretreated rats showed lower levels of oxidative stress and inflammation and doses of 30 or 40 mg/kg slightly reduced neuronal apoptosis and necrosis. These findings suggest that cannabis constituents do not enhance the neurotoxic effects of ketamine and might partly counteract the effects of ketamine-induced NMDA antagonism by reducing the release of free radicals and inflammatory mediators in brain

scholarly journals DietaryN-acetylcysteine supplementation alleviates liver injury in lipopolysaccharide-challenged piglets

2013 ◽  
Vol 111 (1) ◽  
pp. 46-54 ◽  
Author(s):  
Dan Yi ◽  
Yongqing Hou ◽  
Lei Wang ◽  
Binying Ding ◽  
Zhengguo Yang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Heat Shock Protein 70 ◽  
Basal Diet ◽  
Control Group ◽  
Saline Injection ◽  
Antioxidative Capacity ◽  
Blood Samples ◽  
Lps Challenge ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

The present study was carried out to determine whetherN-acetylcysteine (NAC) could modulate liver injury in a lipopolysaccharide (LPS)-challenged piglet model. For this purpose, eighteen piglets were randomly assigned to the control, LPS or NAC group. Piglets in the control and LPS groups were fed a basal diet, whereas those in the NAC group were fed the basal diet supplemented with 500 mg/kg NAC. On days 10, 13 and 20 of the trial, the LPS- and NAC-treated piglets were intraperitoneally administered LPS (100 μg/kg body weight), while the control group was administered the same volume of saline. On day 20 of the trial, blood samples were obtained 3 h after LPS or saline injection. On day 21, the piglets were killed to collect liver samples. Dietary NAC supplementation attenuated LPS-induced liver histomorphological abnormalities. Compared with the control group, in the LPS-challenged piglets, the activities of alanine aminotransferase and aspartate aminotransferase and the concentrations of H2O2, TNF-α, IL-6 and PGE2were dramatically increased in the plasma and the activity of superoxide dismutase in the plasma and that of glutathione peroxidase in the liver were significantly decreased. The LPS challenge also increased the concentration of AMP and the ratio of AMP:ATP, but decreased adenylate energy charges and the levels of ATP and ADP. These adverse effects of the LPS challenge were ameliorated by NAC supplementation. Moreover, NAC inhibited the LPS-induced increases in the abundance of liver heat shock protein 70 and NF-κB proteins. In conclusion, these results suggest that dietary NAC supplementation alleviates LPS-induced liver injury by reducing the secretion of pro-inflammatory cytokines, increasing the antioxidative capacity and improving energy metabolism.

A direct requirement of nuclear factor-κB for suppression of apoptosis in ventricular myocytes

2000 ◽  
Vol 279 (3) ◽  
pp. H939-H945 ◽  
Author(s):  
Shareef Mustapha ◽  
Alla Kirshner ◽  
Danielle De Moissac ◽  
Lorrie A. Kirshenbaum
Keyword(s):  
Dna Binding ◽  
Gene Transcription ◽  
Ventricular Myocytes ◽  
Vital Staining ◽  
Fold Increase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Cytoplasmic Factor ◽  
Tnf Α ◽  
Factor Α

Nuclear factor-κB (NF-κB) is a ubiquitously expressed cellular factor regulated by the cytoplasmic factor inhibitor protein κBα (IκBα). Activation of NF-κB by cytokines, including tumor necrosis factor-α (TNF-α), requires the phosphorylation and degradation of IκBα. An anti-apoptotic role for NF-κB has recently been suggested. In the present study, we ascertained whether death-promoting signals and apoptosis mediated by TNF-α are suppressed by NF-κB in postnatal ventricular myocytes. Stimulation of myocytes with TNF-α resulted in a 12.1-fold increase ( P < 0.01) in NF-κB-dependent gene transcription and DNA binding compared with controls. This was accompanied by a corresponding increase in the NF-κB target protein A20 as determined by Western blot analysis. Vital staining revealed that TNF-α was not cytotoxic to myocytes and did not provoke apoptosis. Adenovirus-mediated delivery of a nonphosphorylatable form of IκBα to inactivate NF-κB prevented TNF-α-stimulated NF-κB-dependent gene transcription and nuclear NF-κB DNA binding. Importantly, myocytes stimulated with TNF-α and defective for NF-κB activation resulted in a 2.2-fold increase ( P < 0.001) in apoptosis. To our knowledge, the data provide the first indication that a functional NF-κB signaling pathway is crucial for suppressing death-promoting signals mediated by TNF-α in ventricular myocytes.

scholarly journals The Effects of Rice Husk Liquid Smoke in Porphyromonas gingivalis-Induced Periodontitis

2021 ◽  
Author(s):  
Theresia Indah Budhy ◽  
Ira Arundina ◽  
Meircurius Dwi Condro Surboyo ◽  
Anisa Nur Halimah
Keyword(s):  
Growth Factor ◽  
Porphyromonas Gingivalis ◽  
Rice Husk ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Control Group ◽  
Proliferation Markers ◽  
Liquid Smoke ◽  
Tnf Α ◽  
Factor Α

Abstract Objectives The purpose of this study is to analyze the effects of rice husk liquid smoke in Porphyromonas gingivalis-induced periodontitis in the inflammatory and proliferation marker such as nuclear factor kappa β (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), fibroblast growth factor 2 (FGF2), collagen type 1 (COL-1) expression, and the number of macrophages, lymphocytes, and fibroblasts. Materials and Methods Rice husk liquid smoke is obtained by the pyrolysis process. Porphyromonas gingivalis-induced periodontitis in 20 μL phosphate-buffered saline containing 1 × 109 CFU was injected into the lower anterior gingival sulcus of Wistar rats. The periodontitis was then treated with 20 μL/20 g body weight of rice husk liquid smoke once a day for 2 and 7 days, respectively. After treatment, the bone and lower anterior gingival sulcus were analyzed with immunohistochemistry and hematoxylin–eosin staining. Results The treatment of periodontitis with rice husk liquid smoke showed a lower NF-kB, TNF-α, and IL-6 expression and a higher TGF-β, FGF2, and COL-1 expression than the control after treatment for 2 and 7 days (p < 0.05), respectively. The number of macrophages and fibroblasts was also higher when compared with the control group (p < 0.05), but the number of lymphocytes was lower than the control (p < 0.05). Conclusion Rice husk liquid smoke showed its effects on Porphyromonas gingivalis-induced periodontitis with a decrease in inflammatory markers and an increase in proliferation markers. The development of a rice husk liquid smoke periodontitis treatment is promising.

scholarly journals Simultaneous Inhibition of Three Major Cytokines and Its Therapeutic Effects: A Peptide-Based Novel Therapy against Endotoxemia in Mice

2021 ◽  
Vol 11 (5) ◽  
pp. 436
Author(s):  
Hung-Jen Shih ◽  
Chao-Yuan Chang ◽  
Milton Chiang ◽  
Van Long Le ◽  
Hao-Jen Hsu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Therapeutic Effects ◽  
The Novel ◽  
Tissue Water ◽  
Novel Therapy ◽  
Binding Domains ◽  
Tnf Α ◽  
Simultaneous Inhibition ◽  
Factor Α ◽  
Liver Tissues

Three major cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, mediate endotoxemia-induced liver injury. With the similar structures to the binding domains of the three cytokines to their cognate receptors, the novel peptide KCF18 can simultaneously inhibit TNF-α, IL-1β, and IL-6. We elucidated whether KCF18 can alleviate injury of liver in endotoxemic mice. Adult male mice (BALB/cJ) were intraperitoneally (i.p.) administered lipopolysaccharide (LPS, 15 mg/kg; LPS group) or LPS with KCF18 (LKCF group). Mice in the LKCF group received KCF18 (i.p.) at 2 h (0.6 mg/kg), 4 h (0.3 mg/kg), 6 h (0.3 mg/kg), and 8 h (0.3mg/kg) after LPS administration. Mice were sacrificed after receiving LPS for 24 h. Our results indicated that the binding levels of the three cytokines to their cognate receptors in liver tissues in the LKCF group were significantly lower than those in the LPS group (all p < 0.05). The liver injury level, as measured by performing functional and histological analyses and by determining the tissue water content and vascular permeability (all p < 0.05), was significantly lower in the LKCF group than in the LPS group. Similarly, the levels of inflammation (macrophage activation, cytokine upregulation, and leukocyte infiltration), oxidation, necroptosis, pyroptosis, and apoptosis (all p < 0.05) in liver tissues in the LKCF group were significantly lower than those in the LPS group. In conclusion, the KCF18 peptide–based simultaneous inhibition of TNF-α, IL-1β, and IL-6 can alleviate liver injury in mice with endotoxemia.

scholarly journals Association of Tumor Necrosis Factor-α -308G>A, -238G>A and -376G>A polymorphisms with recurrent pregnancy loss risk in the Greek population

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sofoklis Stavros ◽  
Despoina Mavrogianni ◽  
Myrto Papamentzelopoulou ◽  
Evaggelos Basamakis ◽  
Hend Khudeir ◽  
...  
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Pcr Amplification ◽  
Greek Population ◽  
Control Group ◽  
Increased Risk ◽  
Tnf Α ◽  
Caucasian Women ◽  
Factor Α ◽  
And Control

Abstract Background Promoter region SNPs in TNF-α have been studied in association with Recurrent Pregnancy Loss (RPL) occurrence in various populations. Among them, −238G > A, −308G > A and − 376G > A have been frequently investigated for their potential role in recurrent abortions. The aim of the present study is to evaluate the correlation among TNF-α 238, TNF-α 308 and TNF-α 376 polymorphisms and recurrent pregnancy loss risk in Greek women. Methods This study included 94 Caucasian women with at least two miscarriages of unexplained aetiology, before the 20th week of gestation. The control group consisted of 89 Caucasian women of proven fertility, with no history of pregnancy loss. DNA samples were subjected to PCR amplification using specific primers. Sanger sequencing was applied to investigate the presence of TNF-α 238, TNF-α 308, TNF-α 376 polymorphisms in all samples. Results The TNF-α 238 and TNF-α 308 variants were both detected in RPL and control groups (7.45% vs 4.49 and 45.16% vs 36.73%, respectively), but with no statistically significant association (p-value 0.396 and 0.374, respectively). The TNF-α 376 variant was not detected at all in both control and RPL groups. When TNF-α 238 and TNF-α 308 genotypes were combined no association with RPL was detected (p-value = 0.694). In subgroup analysis by parity, RPL patients carrying the A allele reported less previous births. Conclusions This is the first study demonstrating TNF-α 238 and TNF-α 308 gene expression and the absence of TNF-α 376 variant in Greek women with RPL. However, no association emerged between each polymorphism studied and the occurrence of recurrent pregnancy loss. Accordingly, TNF-α -308G > A, −238G > A and -376G > A variants are not considered genetic markers for identifying women at increased risk of recurrent pregnancy loss in the Greek population.

scholarly journals Altered Expression of Hematopoiesis Regulatory Genes in the Bone Marrow Mesenchymal Stem Cells of Patients of Aplastic Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3904-3904
Author(s):  
Soniya Nityanand ◽  
Naresh Kumar Tripathy ◽  
Chandra Prakash Chaturvedi ◽  
Ekta Minocha ◽  
Akhilesh Sharma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Fold Increase ◽  
Regulatory Genes ◽  
Control Group ◽  
Medical Sciences ◽  
Post Graduate ◽  
Tnf Α ◽  
Post Graduate Institute

Abstract Mesenchymal stem cells (MSC) are an important component of the hematopoietic niche in the bone marrow (BM) and regulate hematopoiesis by producing a variety of cytokines and growth factors. In aplastic anemia (AA), most of the studies have attributed the reduced hematopoiesis to a defect in hematopoietic stem cells (HSC) and limited data is available on the role of BM-MSC in AA. Therefore, the objective of the present study was to evaluate the expression of hematopoiesis regulatory genes, viz. granulocyte colony stimulating factor (G-CSF), stromal cell derived factor (SDF-1), stem cell factor (SCF), tumor necrosis factor-alpha (TNF-α) macrophage inflammatory protein-1 alpha (MIP-1α) and transforming growth factor-beta (TGF-β) in BM-MSC of patients with AA and compare it with BM-MSC of control group. Twenty patients of idiopathic acquired AA with a median age of 25.5 years (range: 12-64 years) were included in the study. The control group consisted of 10 healthy volunteers and 10 patients with iron deficiency anemia or immune thrombocytopenic purpura. The median age of the control group was 20 years (range: 11-62 years). The BM-MSC were isolated and cultured as per protocol standardized and previously published by us. Third passage cells were used in the study. The MSC were characterized both by their phenotypic markers and by their ability to differentiate into adipogenic and osteogenic lineages. The expression of hematopoiesis regulatory genes was studied by real-time quantitative polymerase chain reaction (qRT-PCR). The GAPDH was used as the housekeeping gene to normalize the transcript levels and the fold change in the gene expression was calculated by 2-ΔΔCtmethod. The BM-MSC of AA patients and controls had similar morphology and expression of mesenchymal markers CD73, CD105, CD90 and CD166, absence of expression of hematopoietic markers CD13, CD34 and CD45 and of HLA-DR. However, the BM-MSC of AA patients exhibited a higher adipogenic and a lower osteogenic differentiation in comparison to those of controls. Further, the BM-MSC of AA patients in comparison to those of control group, had a higher expression of G-CSF (fold increase: 1.99; p<0.0001), SDF-1 (fold increase: 1.37; p<0.01) and TNF-α (fold increase: 10.68; p<0.0001) and a very low expression of MIP-1α (fold decease: 50.0; p<0.0001) transcripts. The expression of SCF and TGF-β transcripts were comparable in the BM-MSC of both the groups (p>0.05). Though AA patients have been shown to have elevated levels of G-CSF in the peripheral blood and BM but there is only one previous report on G-CSF gene expression in BM-MSC of AA, in which a higher expression was observed and thus corroborates with our data. There is no data available on SDF-1 levels in the peripheral blood and bone marrow of AA patients. We have observed higher gene expression of SDF-1 in BM-MSC of AA patients. The higher expression of G-CSF and SDF-1, pro-hematopoietic factors, in AA may be due to a compensatory response of the BM stroma to boost the hematopoiesis. Our observation of higher TNF-α gene expression in BM-MSC corroborates with previous reports on higher levels of this anti-hematopoietic cytokine in the BM plasma of patients with AA and indicates that MSC could contribute to the increase in the TNF-α level in the BM of AA patients. A conspicuous observation of our study was a markedly decreased expression of MIP-1α gene in BM-MSC of AA and to the best of our knowledge this is the first report on MIP-1α in AA. MIP-1α is a chemokine which has been shown to inhibit proliferation of HSC in vitro and thus may help to maintain HSC in an undifferentiated state. Furthermore, MIP-1α has also been reported to mediate interaction of HSC with stromal cells in BM and may have a role in supporting hematopoiesis. Its precise role in AA needs to be studied further. We are currently studying the levels of these cytokines/growth factors in the BM plasma of the same cohort of AA patients and controls and the data will be presented. Our study thus shows that BM-MSC of AA patients have altered expression of hematopoiesis regulatory genes which may contribute to the pathobiology of the disease. Disclosures Nityanand: Sanjay Gandhi Post Graduate Institute of Medical Sciences: Employment, Research Funding. Tripathy:Sanjay Gandhi Post Graduate Institute of Medical Sciences: Employment. Chaturvedi:Dept of Biotechnology, Govt of India: Employment. Minocha:Dept of Science and Technology, Govt of India: Other: PhD scholarship. Sharma:Sanjay Gandhi Post Graduate Institute of Medical Sciences: Employment. Rahman:SGPGI, Lucknow , India: Employment, Research Funding.

scholarly journals The Immuno modulatory Changes of Patients with Tuberculosis.

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Rafal J Al-Saigh ◽  
Hussam Al-Humadi
Keyword(s):  
Rural Areas ◽  
Liver Function Tests ◽  
Pulmonary Diseases ◽  
Control Group ◽  
Chronic Obstructive ◽  
Descriptive Data ◽  
Tnf Α ◽  
Significant Difference ◽  
Level Versus ◽  
Factor Α

Tuberculosis(TB) is aninfectious disease caused by Mycobacterium tuberculosis. The aim was to investigate the levels of immunomodulatory markers like interluekin-6 (IL-6), tumor necrotizing factor-α (TNF- α),cell differentiation-4 (CD4) and CD8 levels in those patients with active tuberculosis (TB) disease in comparison with control group. 41 Adults diagnosed with TB were included in comparison to 32 healthy individuals at Babylon health center for pulmonary diseases and TB. Descriptive data for patients and control group werecollected by well-trained researcher following a structured questionnaire. In parallel, peripheral blood collected to determine IL-6, TNF- α,CD4 and CD8. Then the assessment for the association between clinical and descriptive data and immunomodulatory markers levels was investigated statistically. The majority of TB patients were males (56%) and 71% were resident in rural areas; 47% of them were living in middle socioeconomic state,moreover,47% of TB cases had diabetes,furthermore,51% had chronic obstructive pulmonary diseases,12% had hypertension and 39% of them had chronic anemia with 47% smokers with no significant difference versus control. Following to that,there was highly increased in IL-6 and TNF-α levels in TB patients versus control (P<0.001),with low CD4 level versus control (P<0.001). While there was no significant change shown in CD8 levels versus control and this might highly be correlated with 30% of abnormal liver function tests among TB patients. A high proportion of TB patients have low CD4 level mostly associated with active disease. Moreover,the increase of IL-6 and TNF-α levels suggests a inverse impact on CD4 level which closely associated with the outcome of the disease.

scholarly journals Analysis on the Expression and Prognostic Value of LncRNA FAF in Patients with Coronary Heart Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Hai Xu ◽  
Xiwen Zhang ◽  
Kun Yu ◽  
Gang Zhang ◽  
Yafei Shi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
High Sensitivity ◽  
Control Group ◽  
Coronary Lesion ◽  
Tnf Α ◽  
Factor Α

Objective. To investigate the expression and prognostic value of LncRNA FAF in patients with coronary heart disease. Patients and Methods. 97 patients with coronary heart disease who came to our hospital were selected as the research group (RG), and 97 healthy people who came to our hospital for physical examination during the same period were selected as the control group (CG). The serum LncRNA FAF, plasma homocysteine (HCY), lipoprotein A (Lp-a), serum tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) in the two groups of patients were detected, and their correlations were analyzed. Then, the predictive value and risk factors of FAF for poor prognosis of patients with coronary heart disease were analyzed. Results. The expression of LncRNA FAF in the serum of patients in the RG was significantly lower than that in the CG, and the expressions of HCY, Lp-a, TNF-α, and hsCRP were significantly higher than those in the CG (p <0.05). The AUC of FAF in the diagnosis of coronary heart disease was more than 0.9. FAF was negatively correlated with the coronary lesion vessels, HCY, Lp-a, TNF-α, and hsCRP expressions in patients with coronary heart disease ( p < 0.05 ). The ROC of FAF for predicting poor prognosis in patients with coronary heart disease was greater than 0.9. Low expression of FAF; high expressions of HCY, Lp-a, and hsCRP; and increase of coronary lesion vessels were independent risk factors for poor prognosis in patients with coronary heart disease. Conclusions. LncRNA FAF was lowly expressed in the serum of patients with coronary heart disease, and it was of high value in the diagnosis and prediction of poor prognosis of coronary heart disease. It was also an independent risk factor for poor prognosis of patients with coronary heart disease and may be a potential target for diagnosis and treatment of coronary heart disease.

scholarly journals Lactobacillus reuteri ZJ617 Culture Supernatant Attenuates Acute Liver Injury Induced in Mice by Lipopolysaccharide

2019 ◽  
Vol 149 (11) ◽  
pp. 2046-2055 ◽  
Author(s):  
Yanjun Cui ◽  
Sirui Qi ◽  
Wenming Zhang ◽  
Jiangdi Mao ◽  
Renlong Tang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Intraperitoneal Injection ◽  
Molecular Mechanisms ◽  
Culture Supernatant ◽  
Lactobacillus Reuteri ◽  
Acute Liver Injury ◽  
Saline Control ◽  
Control Group ◽  
Intestinal Integrity ◽  
Oral Inoculation

ABSTRACT Background Lactobacillus rhamnosus GG culture supernatant (LGGs) promotes intestinal integrity and ameliorates acute liver injury induced by alcohol in mice. Objectives The aim of this study was to investigate the protective effects and molecular mechanisms of Lactobacillus reuteri ZJ617 culture supernatant (ZJ617s) on acute liver injury induced by lipopolysaccharide (LPS) in mice. Methods Male C57BL/6 mice (20 ± 2 g, 8 wk old) were randomly divided into 4 groups (6 mice/group): oral inoculation with phosphate-buffered saline (control), intraperitoneal injection of LPS (10 mg/kg body weight) (LPS), oral inoculation with ZJ617s 2 wk before intraperitoneal injection of LPS (ZJ617s + LPS), or oral inoculation with LGGs 2 wk before intraperitoneal injection of LPS (LGGs + LPS). Systemic inflammation, intestinal integrity, biomarkers of hepatic function, autophagy, and apoptosis signals in the liver were determined. Results Twenty-four hours after LPS injection, the activities of serum alanine transaminase and aspartate transaminase were 32.2% and 30.3% lower in the ZJ617s + LPS group compared with the LPS group, respectively (P < 0.05). The ZJ617s + LPS group exhibited higher intestinal expression of claudin 3 (62.5%), occludin (60.1%), and zonula occludens 1 (60.5%) compared with the LPS group (P < 0.05). The concentrations of hepatic interleukin-6 and tumor necrosis factor-α were 21.4% and 27.3% lower in the ZJ617s + LPS group compared with the LPS group, respectively (P < 0.05). However, the concentration of interleukin-10 was 22.2% higher in the ZJ617s + LPS group. LPS increased the expression of Toll-like receptor 4 (TLR4; by 50.5%), phosphorylation p38 mitogen-activated protein kinase (p38MAPK; by 57.1%), extracellular signal-regulated kinase (by 77.8%), c-Jun N-terminal kinase (by 42.9%), and nuclear factor-κB (NF-κB; by 36.0%) compared with the control group. Supplementation with ZJ617s or LGGs ameliorated these effects (P < 0.05). Moreover, the hepatic expression of active caspase-3 and microtubule-associated protein 1 light chain 3 II was 23.8% and 28.6% lower in the ZJ617s + LPS group compared with the LPS group, respectively (P < 0.05). Conclusions ZJ617s exerts beneficial effects on the mouse liver through suppression of hepatic TLR4/MAPK/NF-κB activation, apoptosis, and autophagy. This trial was registered at Zhejiang University (http://www.lac.zju.edu.cn) as NO.ZJU20170529.

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