Metabolic changes in rat serum after administration of suberoylanilide hydroxamic acid and discriminated by SVM

2017 ◽  
Vol 36 (12) ◽  
pp. 1286-1294 ◽  
Author(s):  
J Yu ◽  
H Wu ◽  
Z Lin ◽  
K Su ◽  
J Zhang ◽  
...  
Keyword(s):  
Hydroxamic Acid ◽  
Saturated Fatty Acids ◽  
Metabolic Changes ◽  
Gas Chromatography Mass Spectrometry ◽  
Support Vector ◽  
Control Group ◽  
Intragastric Administration ◽  
Suberoylanilide Hydroxamic Acid ◽  
Rat Serum ◽  
Cycle Arrest

Suberoylanilide hydroxamic acid (SAHA) exerts marked anticancer effects via promotion of apoptosis, cell cycle arrest, and prevention of oncogene expression. In this study, serum metabolomics and artificial intelligence recognition were used to investigate SAHA toxicity. Forty rats (220 ± 20 g) were randomly divided into control and three SAHA groups (low, medium, and high); the experimental groups were treated with 12.3, 24.5, or 49.0 mg kg−1 SAHA once a day via intragastric administration. After 7 days, blood samples from the four groups were collected and analyzed by gas chromatography–mass spectrometry, and pathological changes in the liver were examined using microscopy. The results showed that increased levels of urea, oleic acid, and glutaconic acid were the most significant indicators of toxicity. Octadecanoic acid, pentadecanoic acid, glycerol, propanoic acid, and uric acid levels were lower in the high SAHA group. Microscopic observation revealed no obvious damage to the liver. Based on these data, a support vector machine (SVM) discrimination model was established that recognized the metabolic changes in the three SAHA groups and the control group with 100% accuracy. In conclusion, the main toxicity caused by SAHA was due to excessive metabolism of saturated fatty acids, which could be recognized by an SVM model.

scholarly journals Urinary Volatomic Expression Pattern: Paving the Way for Identification of Potential Candidate Biosignatures for Lung Cancer

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 36
Author(s):  
Khushman Taunk ◽  
Priscilla Porto-Figueira ◽  
Jorge A. M. Pereira ◽  
Ravindra Taware ◽  
Nattane Luíza da Costa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Fatty Acid Biosynthesis ◽  
Solid Phase ◽  
Partial Least Square ◽  
Least Square ◽  
Gas Chromatography Mass Spectrometry ◽  
Support Vector ◽  
Control Group ◽  
Potential Candidate ◽  
Metabolic Pathway Analysis

The urinary volatomic profiling of Indian cohorts composed of 28 lung cancer (LC) patients and 27 healthy subjects (control group, CTRL) was established using headspace solid phase microextraction technique combined with gas chromatography mass spectrometry methodology as a powerful approach to identify urinary volatile organic metabolites (uVOMs) to discriminate among LC patients from CTRL. Overall, 147 VOMs of several chemistries were identified in the intervention groups—including naphthalene derivatives, phenols, and organosulphurs—augmented in the LC group. In contrast, benzene and terpenic derivatives were found to be more prevalent in the CTRL group. The volatomic data obtained were processed using advanced statistical analysis, namely partial least square discriminative analysis (PLS-DA), support vector machine (SVM), random forest (RF), and multilayer perceptron (MLP) methods. This resulted in the identification of nine uVOMs with a higher potential to discriminate LC patients from CTRL subjects. These were furan, o-cymene, furfural, linalool oxide, viridiflorene, 2-bromo-phenol, tricyclazole, 4-methyl-phenol, and 1-(4-hydroxy-3,5-di-tert-butylphenyl)-2-methyl-3-morpholinopropan-1-one. The metabolic pathway analysis of the data obtained identified several altered biochemical pathways in LC mainly affecting glycolysis/gluconeogenesis, pyruvate metabolism, and fatty acid biosynthesis. Moreover, acetate and octanoic, decanoic, and dodecanoic fatty acids were identified as the key metabolites responsible for such deregulation. Furthermore, studies involving larger cohorts of LC patients would allow us to consolidate the data obtained and challenge the potential of the uVOMs as candidate biomarkers for LC.

Fisher Discrimination of Metabolic Changes in Rats Treated with Aspirin and Ibuprofen

Pharmacology ◽  
2017 ◽  
Vol 100 (3-4) ◽  
pp. 194-200 ◽  
Author(s):  
Jing Zhang ◽  
Huanchun Song ◽  
Shuying Jiang ◽  
Zhibin Chen ◽  
Shuhua Tong ◽  
...  
Keyword(s):  
Liver Function ◽  
Liver Function Tests ◽  
Gas Chromatography Mass Spectrometry ◽  
Control Group ◽  
Intragastric Administration ◽  
Acetoacetic Acid ◽  
Toxic Reaction ◽  
Function Tests ◽  
Metabolomic Data ◽  
Aspirin Group

Background: Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. Methods: A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks. Liver function tests were performed and blood metabonomics were analyzed by gas chromatography-mass spectrometry. Results: The most important compounds altered were trihydroxybutyric acid and l-alanine in the aspirin group, and acetoacetic acid, l-alanine, and trihydroxybutyric acid in the ibuprofen group. With respect to metabolic profiles, all 3 groups were completely distinct from one another. Fisher discrimination showed that 91.1% of the original grouped cases were correctly classified by the third week. However, only 55.6% of liver function tests were able to classify grouped cases correctly. Conclusion: Trihydroxybutyric acid, l-alanine, and acetoacetic acid were the most significant indicators of altered serum metabolites following intragastric administration of aspirin and ibuprofen in rates. These metabolomic data may be used for classification of aspirin and ibuprofen toxicity.

scholarly journals Serum Metabolomic Analysis of Radiation-Induced Lung Injury in Rats

Dose-Response ◽  
2022 ◽  
Vol 20 (1) ◽  
pp. 155932582110670
Author(s):  
Yahui Feng ◽  
Yiying Gao ◽  
Wenling Tu ◽  
Yang Feng ◽  
Jianping Cao ◽  
...  
Keyword(s):  
Lung Injury ◽  
Gas Chromatography Mass Spectrometry ◽  
Control Group ◽  
Sprague Dawley ◽  
Rat Serum ◽  
Cancer Breast ◽  
Sprague Dawley Rats ◽  
Benzyl Thiocyanate ◽  
Significant Enrichment ◽  
Radiation Induced

Radiation-induced lung injury is a common complication of radiotherapy for lung cancer, breast cancer, esophageal cancer, and thymoma. This study aims to illustrate biomarkers of radiation-induced lung injury and its potential mechanism through the study of metabolomic alterations in serum of Sprague-Dawley rats with different radiation doses. Serum from 0, 10, or 20 Gy irradiated rats were collected and subjected to gas chromatography-mass spectrometry. The result showed that there were 23 dysregulated metabolites between the 10 Gy irradiation group and the 0 Gy control group, whereas 36 preferential metabolites were found between the 20 Gy irradiated rat serum and the control groups. Among them, there were 19 common differential metabolites in the 2 irradiation groups, including 3 downregulated (benzyl thiocyanate, carbazole, and N-formyl-L-methionine) and 16 upregulated metabolites. We further analyzed the metabolic pathways of different metabolites; the results showed that there were 3 significant enrichment pathways in the 10 Gy vs 0 Gy group and 7 significant enrichment pathways in the 20 Gy vs 0 Gy group. Among them, taurine and hypotaurine metabolism, riboflavin metabolism, and glyoxylate and dicarboxylate metabolism were the common metabolic enrichment pathways of the 10 Gy vs 0 Gy group and the 20 Gy vs 0 Gy group.

scholarly journals Comprehensive Evaluation of Caloric Restriction-Induced Changes In The Metabolome Profile of Mice

2021 ◽  
Author(s):  
Dadi Xie ◽  
Jinxi Huang ◽  
Qiang Zhang ◽  
Shiyuan Zhao ◽  
Hongjia Xue ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Aspartic Acid ◽  
Comprehensive Evaluation ◽  
Low Cost ◽  
Octadecenoic Acid ◽  
Metabolic Changes ◽  
Gas Chromatography Mass Spectrometry ◽  
Kidney Cortex ◽  
Control Group ◽  
Health Maintenance

Abstract Objects: Caloric restriction (CR) is known to extend lifespan and exert a protective effect on organs, and is thus a low-cost and easily implemented approach to the health maintenance. However, there have been no studies that have systematically evaluated the metabolic changes that occur in the main tissues affected by CR. This study aimed to explore the target tissues metabolomic profile in CR mice.Methods: Male C57BL/6J mice were randomly allocated to the CR group (n = 7) and control group (n = 7). A non-targeted gas chromatography–mass spectrometry (GC–MS) approach and multivariate analysis were used to identify metabolites in the main tissues (serum, heart, liver, kidney, cortex, hippocampus, lung, muscle, and white adipose) in model of CR. Results: We identified 10 metabolites in the heart that showed differential abundance between the 2 groups, along with 9 in kidney, 7 in liver, 6 in lung, 6 in white adipose, 4 in hippocampus, 4 in serum, 3 in cortex, and 2 in muscle. The most significantly altered metabolites were amino acids (AAs) (glycine, aspartic acid, l-isoleucine, l-proline, l-aspartic acid, l-serine, l-hydroxyproline, l-alanine, l-valine, l-threonine, l-glutamic acid, and phenylalanine) and fatty acids (FAs) (palmitic acid, 1-monopalmitin, glycerol monostearate, docosahexaenoic acid, 16-octadecenoic acid, oleic acid, stearic acid, and hexanoic acid). These metabolites were associated with 8 different functional pathways related to the metabolism of AAs, lipids, and energy. Conclusion: Our results provide insight into the specific metabolic changes that are induced by CR and can serve as a reference for physiologic studies on how CR improves health and extends lifespan.

36 EFFECT OF SUBEROYLANILIDE HYDROXAMIC ACID TREATED DONOR CELLS ON DOG CLONING

2015 ◽  
Vol 27 (1) ◽  
pp. 110
Author(s):  
M. J. Kim ◽  
H. J. Oh ◽  
G. A. Kim ◽  
H. N. Suh ◽  
Y. K. Jo ◽  
...  
Keyword(s):  
Hydroxamic Acid ◽  
Developmental Competence ◽  
Control Group ◽  
Suberoylanilide Hydroxamic Acid ◽  
Donor Cells ◽  
Deacetylase Inhibitor ◽  
Significant Difference ◽  
Chi Squared ◽  
Cloned Dog

Although dog cloning technology has been applied to conservation of endangered canids, propagation of elite dogs and production of transgenic dogs, the efficiency of cloning is still very low. To help overcome this problem, we evaluated the effect of treating donor cells with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), on dog cloning efficiency. Relative mRNA expression of the bax1, bcl2, and Dnmt1 in fibroblasts treated with different concentrations (0, 1, 10, 50 μM) of SAHA and durations (0, 20, 44 h) were assessed using real-time polymerase chain reaction. After determining an optimum concentration and duration, histone acetylation levels (H3K9, H4K5/K8/K12/K16) of SAHA-treated cells were analysed using immunostaining. The SAHA-treated cells were used as donor cells for somatic cell nuclear transfer, and activated reconstructed embryos were transferred to recipients. Pregnancy diagnosis was performed by ultrasonography at least 29 days after the embryo transfer. All experiments were repeated more than 3 times and the data were analysed using Graph Prism software (GraphPad Software Inc., San Diego, CA, USA). An unpaired t-test was used to compare transcripts levels and fluorescence intensities. A chi-squared test was used to compare the implantation rates. The bax1/bcl2 ratio of the 1 μM SAHA group was similar to that of control but significantly increased in the 10 μM and 50 μM groups. Expression of Dnmt1 was decreased in the 1 μM SAHA group, and the 10 μM and 50 μM groups showed the lowest expression compared with the control group. Although the bax1/blc2 ratio was not affected by the SAHA treatment duration, 20-h treatment group showed significantly decreased Dnmt1 levels compared with control group. As a pan-HDAC inhibitor, 1 μM for 20 h of SAHA treatment significantly increased acetylation of H3K9, H4K5, H4K8, and H4K16. For control and SAHA groups, a total of 76 and 64 cloned embryos were produced and transferred to 7 and 5 recipients, respectively. Three fetuses were diagnosed in both groups but there was no significant difference in the pregnancy rate. In conclusion, although SAHA treatment as used in this study significantly decreased bax/bcl2 and Dnmt1 transcripts of donor nuclei, as well as increased H3 and H4 acetylation, it would not enough to increase in vivo developmental competence of cloned dog embryos.This study was supported by RDA (#PJ008975022014), IPET (#311062–04–3SB010), Research Institute for Veterinary Science and the BK21 plus program.

scholarly journals Suberoylanilide hydroxamic acid enhances the radiosensitivity of lung cancer cells through acetylated wild-type and mutant p53-dependent modulation of mitochondrial apoptosis

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098154
Author(s):  
Kan Wu ◽  
Xueqin Chen ◽  
Xufeng Chen ◽  
Shirong Zhang ◽  
Yasi Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Hydroxamic Acid ◽  
Site Directed Mutagenesis ◽  
Lung Cancer Cells ◽  
Mutant P53 ◽  
Suberoylanilide Hydroxamic Acid ◽  
Mitochondrial Apoptosis ◽  
Wild Type ◽  
Clonogenic Cell

Objective Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has shown potential as a candidate radiosensitizer for many types of cancers. This study aimed to explore the radiosensitization mechanism of SAHA in lung cancer cells. Methods Mutations in p53 were generated by site-directed mutagenesis using polymerase chain reaction. Transfection was performed to generate H1299 cells carrying wild-type or mutant p53. The radiosensitizing enhancement ratio was determined by clonogenic assays. Mitochondrial apoptosis was detected using JC-1 staining and flow cytometry analysis. Results Our results showed that SAHA induced radiosensitization in H1299 cells expressing wild-type p53, p53R175H or p53P223L, but this enhanced clonogenic cell death was not observed in parental H1299 (p53-null) cells or H1299 cells expressing p53 with K120R, A161T and V274R mutations. In SAHA-sensitized cells, mitochondrial apoptosis was induced following exposure to irradiation. Additionally, we observed that a secondary mutation at K120 (K120R) could eliminate p53-mediated radiosensitization and mitochondrial apoptosis. Conclusions The results of this study suggest that wild-type and specific mutant forms of p53 mediate SAHA-induced radiosensitization by regulating mitochondrial apoptosis, and the stabilization of K120 acetylation by SAHA is the molecular basis contributing to radiosensitization in lung cancer cells.

scholarly journals Antioxidant activity of Lactobacillus plantarum NJAU-01 in an animal model of aging

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qingfeng Ge ◽  
Bo Yang ◽  
Rui Liu ◽  
Donglei Jiang ◽  
Hai Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Capacity ◽  
Lactobacillus Plantarum ◽  
Meat Product ◽  
The Other ◽  
Oxidative Stress Marker ◽  
Control Group ◽  
Intragastric Administration ◽  
Aging Effects ◽  
Sterile Saline

Abstract Background Excessive reactive oxygen species (ROS) can cause serious damage to the human body and may cause various chronic diseases. Studies have found that lactic acid bacteria (LAB) have antioxidant and anti-aging effects, and are important resources for the development of microbial antioxidants. This paper was to explore the potential role of an antioxidant strain, Lactobacillus plantarum NJAU-01 screened from traditional dry-cured meat product Jinhua Ham in regulating D-galactose-induced subacute senescence of mice. A total of 48 specific pathogen free Kun Ming mice (SPF KM mice) were randomly allocated into 6 groups: control group with sterile saline injection, aging group with subcutaneously injection of D-galactose, treatments groups with injection of D-galactose and intragastric administration of 107, 108, and 109 CFU/mL L. plantarum NJAU-01, and positive control group with injection of D-galactose and intragastric administration of 1 mg/mL Vitamin C. Results The results showed that the treatment group of L. plantarum NJAU-01 at 109 CFU/mL showed higher total antioxidant capacity (T-AOC) and the antioxidant enzymatic activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) than those of the other groups in serum, heart and liver. In contrast, the content of the oxidative stress marker malondialdehyde (MDA) showed lower levels than the other groups (P < 0.05). The antioxidant capacity was improved with the supplement of the increasing concentration of L. plantarum NJAU-01. Conclusions Thus, this study demonstrates that L. plantarum NJAU-01 can alleviate oxidative stress by increasing the activities of enzymes involved in oxidation resistance and decreasing level of lipid oxidation in mice.

scholarly journals Metabolic changes following transcatheter bariatric embolotherapy for weight loss in obesity: secondary outcomes from a prospective RCT

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fried ◽  
V.Y Reddy ◽  
P Neuzil ◽  
R Rosen ◽  
P Sramkova ◽  
...  
Keyword(s):  
Weight Loss ◽  
Metabolic Changes ◽  
Exclusion Criterion ◽  
Control Group ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Funding Source ◽  
Post Intervention ◽  
Private Company ◽  
C Peptide

Abstract Background/Introduction Obesity and its comorbid conditions (i.e. type II diabetes mellitus, atrial fibrillation, coronary artery disease, hypertension, etc...) is a growing burden globally, however, the current treatments (i.e. bariatric surgery, intragasrtic balloons and/or pharmaceutical therapy) pose substantial risks or are contraindicated for various populations. Transcatheter bariatric embolotherapy of left gastric artery by reducing “hunger” hormones from the gastric fundus is a procedure for weight loss that has been growing in prominence over the last several years, however, to date no randomized-controlled trial has been conducted until our study. We studied TBE in a double-blind, sham procedure, first in human RCT of patients (pts) with obesity. Purpose The purpose of this study was to assess the safety and efficacy of TBE for weight loss in obese patients as well as to evaluate metabolic changes. Methods After IV propofol, eligible pts (age 21–60; BMI 35–50 kg/m2) were randomized 1:1 to Sham (skin nick & 1 hr wait) or TBE. All pts received Lifestyle Therapy (behavioral and diet education). Study staff following the pts were also blinded to treatment. Blood samples for gastrointestinal hormones were collected in EDTA tubes containing a protease inhibitor cocktail and frozen per local laboratory standards. All collected samples were assessed together in two batches at the end of the study. The hormones analyzed included ghrelin, GIP, GLP-1, Visfatin, resistin, PAI-1 (total), Leptin, and C-Peptide. An Oral Glucose Tolerance Test (OGTT) and a diabetes assay was performed at baseline and at 6- and 12-months post-intervention. Note, while diabetes was an exclusion criterion for this study, pre-diabetes was not. Results 44 pts were enrolled, of which 40 pts were randomized equally to the groups, with no major complications in either group. TBE demonstrated superior weight loss over the control group at 6- and 12-months post-intervention in both intention-to-treat and per-protocol analyses. At 6 and 12 months, the TBE group demonstrated a clinically meaningful decrease in glucose 1-hour post-fasting by OGTT. GIP levels in the TBE group increased at a mean of 21%, indicative of an improvement in pre-diabetic milieu. Circulating plasma visfatin levels decreased 20% at 6 months and 26% at 12 months in the TBE group indicating a decrease in body fat. C-Peptide levels were noticeably increased in the TBE group at 6 months possibly indicating improvements in insulin sensitivity and beta-cell function. Conclusion(s) TBE is safe and results in clinically significant weight loss and demonstrated a positive effect on glucose homeostasis in pre-diabetic patients. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Endobar Solutions, LLC

scholarly journals Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
High Fat Diet ◽  
Amplicon Sequencing ◽  
Gas Chromatography Mass Spectrometry ◽  
Control Group ◽  
Rrna Gene ◽  
High Fat ◽  
Underlying Mechanisms ◽  
Insight Into

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

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