scholarly journals Metabolomics Reveals Metabolic Changes Caused by Low-Dose 4-Tert-Octylphenol in Mice Liver

2018 ◽  
Vol 15 (12) ◽  
pp. 2686 ◽  
Author(s):  
Kun Zhou ◽  
Xingwang Ding ◽  
Jing Yang ◽  
Yanhui Hu ◽  
Yun Song ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Serum ◽  
Low Dose ◽  
Liver Weight ◽  
Serum Levels ◽  
Metabolic Changes ◽  
Protein Levels ◽  
Low Concentrations ◽  
Body Weights ◽  
Mice Liver

Background: Humans are constantly exposed to low concentrations of 4-tert-octylphenol (OP). However, studies investigating the effects of low-dose OP on the liver are scarce, and the mechanism of these effects has not been thoroughly elucidated to date. Methods: Adult male institute of cancer research (ICR) mice were exposed to low-dose OP (0, 0.01 and 1 μg/kg/day) for 7 consecutive days. Weights of mice were recorded daily during the experiment. Blood serum levels of OP, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined, and haematoxylin-eosin (HE) staining of the liver was performed. We applied an integrated metabolomic and enzyme gene expression analysis to investigate liver metabolic changes, and the gene expression of related metabolic enzymes was determined by real-time PCR and ELISA. Results: OP in blood serum was increased after OP exposure, while body weights of mice were unchanged. Liver weight and its organ coefficient were decreased significantly in the OP (1 μg/kg/day) group, but ALT and AST, as well as the HE staining results, were unchanged after OP treatment. The levels of cytidine, uridine, purine and N-acetylglutamine were increased significantly, and the level of vitamin B6 was decreased significantly in mice treated with OP (1 μg/kg/day). The mRNA and protein levels of Cda and Shmt1 were both increased significantly in OP (1 μg/kg/day)-treated mice. Conclusions: Through metabolomic analysis, our study firstly found that pyrimidine and purine synthesis were promoted and that N-acetylglutamine was upregulated after low-dose OP treatment, indicating that the treatment disturbed nucleic acid and amino acid metabolism in mice liver.

Protective Effects of Capparis sepiaria Root Extracts against Acetaminophen-Induced Hepatotoxicity in Wistar Rats

2012 ◽  
Vol 9 (1) ◽  
pp. 1-12 ◽  
Author(s):  
V. Madhavan ◽  
Ajay Shankar Pandey ◽  
Anita Murali ◽  
S. N. Yoganarasimhan
Keyword(s):  
Wistar Rats ◽  
Liver Weight ◽  
Serum Levels ◽  
Organic Analysis ◽  
Protective Effects ◽  
Protein Levels ◽  
Hepatic Transaminases ◽  
Ethanol Extracts ◽  
Hepatoprotective Drug ◽  
Important Drug

Capparis sepiaria L. known as Himsra is an important drug in Ayurveda. In this study extracts of the root of C. sepiaria were evaluated for their hepatoprotective potential on acetaminophen-induced hepatotoxicity in albino Wistar rats. The extent of hepatoprotection was evaluated by estimating the serum levels of hepatic transaminases (SGPT and SGOT), alkaline phosphatase (ALP), total protein (TP), and bilirubin (total and direct). Aqueous and ethanol extracts of C. sepiaria significantly reduced the increased liver weight as well as serum levels of SGPT, SGOT, ALP, and bilirubin, and normalized the reduced serum protein levels in the treated rats. These observations were supported by the results of histopathology studies as well. The extracts were also subjected to preliminary organic analysis and chromatographic studies including HPTLC finger print studies. The results indicate that the roots of C. sepiaria show significant hepatoprotective effect on acetaminophen-induced hepatotoxicity, thus substantiating its use as a potential hepatoprotective drug.

scholarly journals Synergistic benefit in inflammatory arthritis by targeting IκB kinase ϵ and interferon β

2008 ◽  
Vol 68 (2) ◽  
pp. 257-263 ◽  
Author(s):  
M Corr ◽  
D L Boyle ◽  
L Ronacher ◽  
N Flores ◽  
G S Firestein
Keyword(s):  
Gene Expression ◽  
Low Dose ◽  
Serum Levels ◽  
Poly I:C ◽  
Type I ◽  
Wild Type ◽  
Polycytidylic Acid ◽  
Iκb Kinase ◽  
Novel Approach ◽  
Clinical Arthritis

Objectives:The IκB kinase (IKK)-related kinase IKKϵ regulates type I interferon expression and responses as well as proinflammatory mediator production. We examined the role of IKKϵ in arthritis and its ability to enhance the therapeutic response to systemic interferon (IFN) β therapy in passive murine K/BxN arthritis.Methods:IKKϵ–/–, IFNα∼βR–/– and wild type mice were given K/BxN serum and treated with polyinosinic polycytidylic acid (poly(I:C)), IFNβ, or normal saline. Clinical response and histological scores were assessed. Gene expression in the paws was measured by quantitative PCR. Serum interleukin 1a receptor agonist (IL1Ra) and IL10 were measured by ELISA and multiplex bead array.Results:Arthritis was almost completely blocked in wild type mice if arthritogenic K/BxN serum and the Toll-like receptor (TLR)3 ligand, poly(I:C), were coadministered at the onset of the model, but not in established disease. Mice deficient in IFNα∼βR had an accelerated course of arthritis, and did not respond to poly(I:C). IKKϵ null mice had a modest decrease in clinical arthritis compared with heterozygous mice. Low doses of IFNβ that were ineffective in wild type mice significantly decreased clinical arthritis in IKKϵ null mice. Articular chemokine gene expression was reduced in the IKKϵ–/– mice with arthritis and secreted IL1Ra (sIL1Ra) mRNA was significantly increased. Serum levels of IL1Ra were increased in low dose IFNβ-treated IKKϵ–/– mice.Conclusions:Subtherapeutic doses of IFNβ enhance the anti-inflammatory effects of IKKϵ deficiency, possibly by increasing production of IL1Ra and unmasking the antichemokine effects. Combination therapy with low dose IFNβ and an IKKϵ inhibitor might improve efficacy of either agent alone and offers a novel approach to RA.

scholarly journals Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells

2015 ◽  
Vol 37 (5) ◽  
pp. 1750-1758 ◽  
Author(s):  
Eleni Stamoula ◽  
Theofanis Vavilis ◽  
Eleni Aggelidou ◽  
Aikaterini Kaidoglou ◽  
Angeliki Cheva ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Cell Fate ◽  
Low Dose ◽  
Mrna Level ◽  
Neuronal Cell ◽  
Cellular Level ◽  
Mrna Levels ◽  
Protein Levels ◽  
Low Concentrations ◽  
Discrete Effect

Background/Aims: Increasing amounts of the neurotransmitter glutamate are associated with excitotoxicity, a phenomenon related both to homeostatic processes and neurodegenerative diseases such as multiple sclerosis. Methods: PC12 cells (rat pheochromocytoma) were treated with various concentrations of the non-essential amino acid glutamate for 0.5-24 hours. The effect of glutamate on cell morphology was monitored with electron microscopy and haematoxylin-eosin staining. Cell survival was calculated with the MTT assay. Expression analysis of chaperones associated with the observed phenotype was performed using either Western Blotting at the protein level or qRT-PCR at the mRNA level. Results: Administration of glutamate in PC12 cells in doses as low as 10 μM causes an up-regulation of GRP78, GRP94 and HSC70 protein levels, while their mRNA levels show the opposite kinetics. At the same time, GAPDH and GRP75 show reduced protein levels, irrespective of their transcriptional rate. On a cellular level, low concentrations of glutamate induce an autophagy-mediated pro-survival phenotype, which is further supported by induction of the autophagic marker LC3. Conclusion: The findings in the present study underline a discrete effect of glutamate on neuronal cell fate depending on its concentration. It was also shown that a low dose of glutamate orchestrates a unique expression signature of various chaperones and induces cell autophagy, which acts in a neuroprotective fashion.

scholarly journals Association of the Adipokines Chemerin, Apelin, Vaspin and Omentin and Their Functional Genetic Variants with Rheumatoid Arthritis

2021 ◽  
Vol 11 (10) ◽  
pp. 976
Author(s):  
Alaa S. Wahba ◽  
Maha E. Ibrahim ◽  
Dina M. Abo-elmatty ◽  
Eman T. Mehanna
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Genetic Variants ◽  
Serum Levels ◽  
Expression Levels ◽  
Protein Levels ◽  
Egyptian Patients ◽  
Gene Expression Levels ◽  
Increased Susceptibility

Adipokines were shown to exert crucial roles in rheumatic diseases. This study aimed to assess the role of chemerin, apelin, vaspin, and omentin adipokines and their genetic variants rs17173608, rs2235306, rs2236242, and rs2274907, respectively, in rheumatoid arthritis (RA) pathogenesis in Egyptian patients. A total of 150 RA patients and 150 healthy individuals were recruited. Blood samples were collected and used for genotyping. Serum was separated and used for expression analysis by quantitative PCR, and various biochemical markers determination by ELISA. Serum protein levels of chemerin and vaspin, as well as their gene expression levels were higher, while those of apelin and omentin were lower in RA patients and were associated with most of RA clinical and laboratory characteristics. G allele of chemerin rs17173608, T allele of vaspin rs2236242, and T allele of omentin rs2274907 were more frequent in RA patients. Serum levels and gene expression levels of chemerin in GG genotype carriers and vaspin in TT genotype group were significantly higher, while those of omentin in TT genotype carriers were significantly lower than RA patients with other genotypes. There was no association between apelin rs2235306 and RA. Chemerin rs17173608, vaspin rs2236242, and omentin rs2274907 polymorphisms were associated with increased susceptibility to RA.

scholarly journals Exploring the Involvement of NLRP3 and IL-1βin Osteoarthritis of the Hand: Results from a Pilot Study

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Antonella Fioravanti ◽  
Sara Tenti ◽  
Megan McAllister ◽  
Melody Chemaly ◽  
Amanda Eakin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Laboratory ◽  
Local Level ◽  
Group Versus ◽  
Serum Levels ◽  
Low Grade ◽  
Hand Osteoarthritis ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1βplays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The aim of this study was to investigate the involvement of IL-1βand the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in patients with EHOA and nonerosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1βand NLRP3, the serum levels of IL-1β, IL-6, IL-17, and tumor necrosis factor- (TNF-)α, and the protein levels of IL-1βand NLRP3. We also assessed the relationships between IL-1βand NLRP3 and clinical, laboratory, and radiological findings. Fifty-four patients with HOA (25 EHOA and 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cell (PBMC) gene and protein expressions of IL-1βand NLRP3 were quantified by quantitative real-time PCR and western blot. IL-1β, IL-6, IL-17, and TNF-αserum levels were determined by ELISA. IL-1βgene expression was significantly reduced (p=0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in the NEHOA group versus the control (p=0.0063) and EHOA groups (p=0.0038). IL-1βserum levels were not significantly different across the groups; IL-6, IL-17, and TNF-αwere not detectable in any sample. IL-1βconcentrations were negatively correlated with the Kellgren-Lawrence score in the whole population (r=−0.446;p=0.0008) and in NEHOA (r=−0.608;p=0.004), while IL-1βgene expression was positively correlated with the number of joint swellings in the EHOA group (r=0.512;p=0.011). Taken together, our results, showing poorly detectable IL-1βconcentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at the local level.

Epigenetic changes of hepatic glucocorticoid receptor in sheep male offspring undernourished in utero

2017 ◽  
Vol 29 (10) ◽  
pp. 1995 ◽  
Author(s):  
Stella Chadio ◽  
Basiliki Kotsampasi ◽  
Stylliani Taka ◽  
Emmanouil Liandris ◽  
Nikolaos Papadopoulos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Liver Weight ◽  
Physiological Changes ◽  
Epigenetic Changes ◽  
Restricted Diet ◽  
Protein Levels ◽  
Maternal Undernutrition ◽  
Gluconeogenic Enzyme

The aim of this study was to characterise the effects of maternal undernutrition during gestation on hepatic gluconeogenic enzyme gene expression and to determine whether such effects are mediated through epigenetic changes in the glucocorticoid receptor (GR). Pregnant ewes were fed a 50% nutrient-restricted diet from Day 0 to 30 (R1) or from Day 31 to 100 of gestation (R2) or a 100% diet throughout gestation (Control). After parturition lambs were fed to appetite. At 10 months of age offspring were euthanised and livers were removed. Maternal undernutrition did not affect offspring bodyweight at birth or at 10 months of age. However, liver weight of males of the R2 group was lower (P < 0.05) in relation to other groups. A significant (P < 0.05) hypomethylation of the hepatic GR promoter was revealed in males of the R2 group and a tendency towards the same in the R1 group, along with increased (P < 0.001) GR gene expression in both restricted groups. A significant increase (P < 0.05) in hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene expression was found in male lambs of both undernourished groups, accompanied by increased (P < 0.01) protein levels, while no differences were detected for glucose-6-phosphatase (G6Pase) mRNA abundance and protein levels. In female lambs, no differences between groups were observed for any parameter studied. These data represent potential mechanisms by which insults in early life may lead to persistent physiological changes in the offspring.

Negative Correlation Between Serum Levels of Homocysteine and Apolipoprotein M

2019 ◽  
Vol 19 (2) ◽  
pp. 120-126
Author(s):  
J. Wei ◽  
Y. Yu ◽  
Y. Feng ◽  
J. Zhang ◽  
Q. Jiang ◽  
...  
Keyword(s):  
Negative Correlation ◽  
Hepg2 Cells ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Apolipoprotein M ◽  
Protein Mass ◽  
Protein Levels ◽  
Phosphoinositide 3 Kinase

Background: Homocysteine (Hcy) has been suggested as an independent risk factor for atherosclerosis. Apolipoprotein M (apoM) is a constituent of the HDL particles. The goal of this study was to examine the serum levels of homocysteine and apoM and to determine whether homocysteine influences apoM synthesis. Methods: Serum levels of apoM and Hcy in 17 hyperhomocysteinemia (HHcy) patients and 19 controls were measured and their correlations were analyzed. Different concentrations of homocysteine (Hcy) and LY294002, a specific phosphoinositide 3- kinase (PI3K) inhibitor, were used to treat HepG2 cells. The mRNA levels were determined by RT-PCR and the apoM protein mass was measured by western blot. Results: We found that decreased serum apoM levels corresponded with serum HDL levels in HHcy patients, while the serum apoM levels showed a statistically significant negative correlation with the serum Hcy levels. Moreover, apoM mRNA and protein levels were significantly decreased after the administration of Hcy in HepG2 cells, and this effect could be abolished by addition of LY294002. Conclusions: resent study demonstrates that Hcy downregulates the expression of apoM by mechanisms involving the PI3K signal pathway.

Brain-derived neurotrophic factor is associated with coronary macrophage infiltrates in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.A Montone ◽  
M Camilli ◽  
M Russo ◽  
M Del Buono ◽  
F Gurguglione ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
C Reactive Protein ◽  
St Segment Elevation ◽  
Protein Levels ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
St Segment

Abstract Background Brain-derived neurotrophic factor (BDNF) is a neurotrophine that plays a key role in the regulation of both central and peripheral nervous system. Moreover, BDNF is secreted in multiple tissues and exerts systemic, autocrine, and paracrine effects in the cardiovascular system. Of importance, BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries and may be involved in thrombus formation. Thus, BDNF has been suggested as an important link between inflammation and thrombosis, potentially involved in the pathogenesis of acute coronary syndrome (ACS). Purpose In our study we aimed at assessing serum levels of BDNF in patients with ACS, evaluating differences according to clinical presentation [ST-segment elevation myocardial infarction (STEMI) vs. Non-ST-segment elevation ACS (NSTE-ACS)]. Moreover, we assessed the presence of optical coherence (OCT)-defined macrophage infiltrates (MØI) in the culprit vessel of ACS patients and evaluated their relationship with BDNF levels. Methods ACS patients were prospectively selected. Blood samples were collected at admission and serum levels of BDNF were subsequently assessed. Presence of OCT-defined MØI along the culprit vessel was assessed. Results 166 ACS patients were enrolled [mean age 65.3±11.9 years, 125 (75.3%) male, 109 STEMI, 57 NSTE-ACS]. Serum levels of BDNF were higher among STEMI patients compared with NSTE-ACS [median (IQR) 2.48 pg/mL (1.54–3.34) vs. 2.12 pg/mL (1.34–2.47), p=0.007], while C-reactive protein levels did not differ between the two groups. OCT assessment was performed in 53 patients and MØI were detected in 27 patients. Of importance, patients with MØI in the culprit vessel had higher levels of BDNF compared with patients without MØI [median (IQR) 2.23 pg/mL (1.38–2.53) vs. 1.41 pg/mL (0.93–2.07), p=0.023], while C-reactive protein levels did not differ between the two groups. Of note, at multivariate regression analysis BDNF levels were independent predictor of MØI [OR: 2.20; 95% CI (1.02–4.74), p=0.043]. Conclusions Serum levels of BDNF may reliable identify the presence of local macrophage inflammatory infiltrates in patients with ACS. Moreover, BDNF levels are higher in patients with STEMI compared with NSTE-ACS. Taken together, these data suggest that BDNF may represent an interesting link between local inflammatory activation and enhanced thrombosis in ACS. BDNF serum levels Funding Acknowledgement Type of funding source: None

scholarly journals PSIV-11 Effects of very low-dose antibiotics on gene expression profiles in ileal mucosa of weaned pigs infected with a pathogenic E. coli

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 286-286
Author(s):  
Kwangwook Kim ◽  
Sungbong Jang ◽  
Yanhong Liu
Keyword(s):  
Gene Expression ◽  
Systemic Inflammation ◽  
Low Dose ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Post Inoculation ◽  
Growth Promoter ◽  
Weaned Pigs ◽  
Ileal Mucosa ◽  
E Coli

Abstract Our previous studies have shown that supplementation of low-dose antibiotic growth promoter (AGP) exacerbated growth performance and systemic inflammation of weaned pigs infected with pathogenic Escherichia coli (E. coli). The objective of this experiment, which is extension of our previous report, was to investigate the effect of low-dose AGP on gene expression in ileal mucosa of weaned pigs experimentally infected with F18 E. coli. Thirty-four pigs (6.88 ± 1.03 kg BW) were individually housed in disease containment rooms and randomly allotted to one of three treatments (9 to 13 pigs/treatment). The three dietary treatments were control diet (control), and 2 additional diets supplemented with 0.5 or 50 mg/kg of AGP (carbadox), respectively. The experiment lasted 18 d [7 d before and 11 d after first inoculation (d 0)]. The F18 E. coli inoculum was orally provided to all pigs with the dose of 1010 cfu/3 mL for 3 consecutive days. Total RNA [4 to 6 pigs/treatment on d 5; 5 to 7 pigs/treatment on 11 post-inoculation (PI)] was extracted from ileal mucosa to analyze gene expression profiles by Batch-Tag-Seq. The modulated differential gene expression were defined by 1.5-fold difference and a cutoff of P &lt; 0.05 using limma-voom package. All processed data were statistically analyzed and evaluated by PANTHER classification system to determine the biological process function of genes in these lists. Compared to control, supplementation of recommended-dose AGP down-regulated genes related to inflammatory responses on d 5 and 11 PI; whereas, feeding low-dose AGP up-regulated genes associated with negative regulation of metabolic process on d 5, but down-regulated the genes related to immune responses on d 11 PI. The present observations support adverse effects of low-dose AGP in our previous study, indicated by exacerbated the detrimental effects of E. coli infection on pigs’ growth rate, diarrhea and systemic inflammation.

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