Metabolic changes in mouse plasma after acute diquat poisoning by UPLC-MS/MS

2020 ◽  
Vol 16 ◽  
Author(s):  
Lianguo Chen ◽  
Zuoquan Zhong ◽  
Jiawen Liu ◽  
Congcong Wen ◽  
Yongxi Jin ◽  
...  

Introduction: Diquat is a fast-acting contact herbicide and plant dehydrating agent. The oral lethal dose 50 (LD50) of diquat in mice is about 125 mg/kg. The purpose of this study is to research the metabolomics in mouse plasma after acute diquat poisoning. Method: These mice were divided into two groups (the control group and acute diquat poisoning group). The control group was given normal saline by gavage. The acute diquat poisoning group was given 50 mg/kg diquat. UPLC-MS/MS was used to determinate the small molecule organic acid in mouse plasma. Results: Compare to the control group, the L-lysine, Adenine, L-Alanine, L-Valine, Lactic acid, Inosine, Adenosine, LTryptophan, L-Tyrosine, L-Arginine, L-Phenylalanine, L-Methionine, Citric acid, Fructose, L-Glutamine, Malic acid, LAspartic acid and Pyruvic acid increased in the acute diquat poisoning group (p<0.05); while the L-Histidine decreased (p<0.05). Conclusion: The results of metabolites increased or decreased, indicating that acute diquat poisoning induced amino acid metabolism and energy metabolism perturbations in mice.

1994 ◽  
Vol 267 (5) ◽  
pp. E672-E679 ◽  
Author(s):  
L. J. Wykes ◽  
J. D. House ◽  
R. O. Ball ◽  
P. B. Pencharz

Low tyrosine solubility in total parenteral nutrition (TPN) solutions complicates meeting the aromatic amino acid needs of infants. This study compared the effectiveness of two tyrosine precursors to supply the aromatic amino acid needs of TPN-fed neonatal piglets with a control group in which total aromatic acid needs were met by the addition of phenylalanine (Phe). Eighteen 3-day-old male Yorkshire piglets (6/group) received TPN for 8 days by central line. The solution was supplemented with Phe or one of the following two tyrosine precursors: N-acetyltyrosine (N-AcTyr) or glycyltyrosine (GlyTyr). Aromatic amino acid metabolism, growth, and nitrogen utilization were measured. Average amino acid and energy intakes were 14.6 g.kg-1.day-1 and 1,050 kJ.kg-1.day-1. Nitrogen balance and utilization were significantly higher (P < 0.05) in piglets in the control Phe group and on the GlyTyr regimen. The high urinary excretion of N-AcTyr (65%) confirms its low bioavailability. Flux and oxidation were significantly higher (P < 0.05) in the Phe group. High plasma Phe levels and excretion of Phe catabolites, as well as the high plasma tyrosine in the GlyTyr group, indicate that current strategies employed to meet the aromatic amino acid needs of neonates on TPN need further refinement.


2021 ◽  
Author(s):  
Yanjuan Liu ◽  
Qi Zeng ◽  
Wen Xiao ◽  
Fang Chen ◽  
Lianhong Zou ◽  
...  

Abstract Xuebijing injection has been widely applied to treat sepsis. However, its roles in the dynamic change of metabolism in sepsis are still unknown. In our study, Gas chromatography-mass spectrometer (GC-MS) combined with multivariate statistical techniques was used to detect the metabolic change in septic rats with or without XBJ injection treatment. The KEGG pathway analysis was used to further analyze the related metabolic pathways in which the identified metabolites were involved. Based on the fold change, variable important in projection, and P value, we found 11, 33 and 26 differential metabolites in the sepsis group at 2, 6 and 12 hours post CLP, compared with the control group. Besides, we also found 32, 23 and 28 differential metabolites in the XBJ group at 2, 6 and 12 hours post CLP. The related pathways of differential metabolites were glycometabolism at 2h, glycometabolism and amino acid metabolism at 6h and amino acid metabolism at 12h post CLP in the sepsis group compared with the control group. Besides, glycometabolism, amino acid metabolism and lipid metabolism changed markedly after XBJ injection for 2 hours; while only amino acid metabolism changed significantly with the treatment of XBJ injection for 6 and 12 hours, compared with the sepsis group. Further analysis showed 3, 6 and 6 differential metabolites were overlapped in the sepsis group and XBJ group at 2, 6 and 12 hours post CLP. These identified differential metabolites were majorly involved in arginine and proline metabolism, suggesting that XBJ injection is capable of improving metabolic disorders in CLP-induced septic rat to a certain extent.


2022 ◽  
Author(s):  
Ye Xiao ◽  
Xiang Lin ◽  
Zhong-Qun Liu ◽  
Mei-Lan Zhou ◽  
Tian-Yu Ren ◽  
...  

Abstract Although diquat is a widely used water-soluble herbicide in the world, its toxicity to freshwater fish has not been well characterized. In this study, gas chromatography-mass spectrometry (GC-MS) based metabolomics approach combined with histopathological examination and biochemical assays was applied to comprehensively assess the hepatotoxicity in zebrafish (Brachydanio rerio) after diquat exposure at two dosages of 0.34 and 1.69 mg·L−1 for 35 days. The results indicated that 1.69 mg·L−1 diquat exposure cause serious cellular swell and vacuolization with increased nuclear abnormality, and lead to obvious disturbance of antioxidative system and dysfunction in liver; while no obvious pathological injury could be detected, and changes in liver biochemistry were less pronounced at the dose level of 0.34 mg·L−1. Multivariate statistical analysis and pattern recognition showed different GC-MS profiles of zebrafish liver following exposure to diquat, the cluster of the treated groups were both clearly separated from the control samples. The differentially abundant metabolites mainly include carbohydrates, amino acids, lipids, nucleotides, and their derivatives. In the exposure group of 1.69 mg·L−1 diquat, severe disturbances of amino acid metabolism played important biological roles associated with inhibition of energy metabolism, reduced immunity, and disorders in neurotransmitters as pathway analysis revealed. Additionally, fluctuation of inositol, creatine, and pantothenic acid, substances associated with stress regulation and signal transduction, participating in metabolic abnormalities in zebrafish with diquat-triggered hepatic damage. Energy metabolism of zebrafish exposed on 0.34 mg·L−1 diquat more inclined to rely on anaerobic glycolysis than the normal ones. Amino acid metabolism responses were less affected, but obvious interference effects on lipid metabolism were observed with 0.34 mg·L−1 diquat exposure. These results imply increased sensitivity of metabolomics versus histopathology and clinical chemistry in recognizing liver toxicity of diquat. This study will contribute to explore possible mechanism of hepatic damages on nontarget freshwater fish induced by diquat and provide important basis for its environmental risk assessment.


2020 ◽  
Vol 17 (8) ◽  
pp. 753-765
Author(s):  
Rui He ◽  
Juntian Liu ◽  
Chang Huang ◽  
Jinyi Liu ◽  
Herong Cui ◽  
...  

Background: Alzheimer's disease (AD) is a common neurodegenerative disorder with the symptoms of cognitive impairment and decreased learning and memory abilities. Metabolomics can reflect the related functional status and physiological and pathological changes in the process of AD. Moxibustion is a unique method in traditional Chinese medicine, which has been used in the treatment and prevention of diseases for thousands of years. Methods: A total of 32 APP/PS1 mice were randomly divided into the model group, moxibustion group, moxa smoke group and smoke-free moxibustion group (n=8/group), using the random number table method, while eight C57BL/6 mice were used as the control group. The five groups were measured for 20 min/day, 6 days/week, for 4 weeks. After 4 weeks’ experiment, all the mice were placed in metabolic cages to collect urine continuously for 24 hours, for UPLC-MS analysis. Results: Principal component analysis (PCA) was used to identify the different metabolites among the five groups, and partial least squares discriminant analysis (PLS-DA) was performed to reveal the effects on the metabolic variance. Sixteen potential biomarkers were identified among the five groups, primarily related to amino acid metabolism, starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, and aminoacyl biosynthesis. There were 17 differences in the potential metabolites between the control and model groups, involving the metabolism of amino acid, purine, pyrimidine, nicotinic acid and nicotinamide, and biosynthesis of pantothenate and coenzyme A. Fifteen potential biomarkers were identified between the model and moxibustion groups, related to starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, glyoxylate, dicarboxylate anions and some amino acid metabolism. Conclusion: Moxibustion can regulate the metabolism of substance and energy by improving the synthesis and decomposition of carbohydrates and amino acids in APP/PS1 transgenic AD model mice.


2017 ◽  
Vol 44 (5) ◽  
pp. 1749-1761 ◽  
Author(s):  
Jie Yin ◽  
Hui Han ◽  
Yuying Li ◽  
Zhaojin Liu ◽  
Yurong Zhao ◽  
...  

Background/Aims: Our previous reports suggested that dietary supplementation with lysine influenced intestinal absorption and metabolism of amino acids. In this study, we further investigated the effect of lysine restriction (30%) on feed intake and we also tested the hypothesis that gut microbiome contributed to the potential mechanism of lysine restriction-mediated feeding behavior. Here, we profiled gut microbial communities by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from gut samples as well as growth performance, serum hormones, and intestinal lysine transport in a piglet model. Results: Piglets preferred to the lysine restricted diet when giving three diets and the feed intake was markedly higher in the lysine-restricted group than that in the control group. Altered hormones (leptin, CCK, and ghrelin) might contribute to the feeding behavior caused by lysine restriction. Meanwhile, lysine transporting ability (SLC7A1 and SLC7A2 expression, intestinal electrophysiological changes, and amino acid pool in mesenteric vein) was decreased in response to lysine restriction. Through deep sequencing of bacterial rRNA markers, we observed that bacterial diversity was enhanced in the lysine-restricted group (Shannon H, PD, and Chao1). At the phylum level, lysine restriction enhanced gut Actinobacteria, Saccharibacteria, and Synergistetes abundances. At the family level, Moraxellaceae, Halomonadaceae, Shewanellaceae, Corynebacteriaceae, Bacillaceae, Comamonadaceae, Microbacteriaceae, Caulobacteraceae, and Synergistaceae abundances were increased in response to lysine restriction. Predictive functional profiling of microbial communities by PICRUSt also confirmed that dietary lysine restriction affected gut microbiome, which might further mediate amino acid metabolism, membrane transport, and endocrine system. Conclusion: Our results indicated that lysine restriction inhibited intestinal lysine transport and promoted feed intake, which might be associated with gut microbiome.


1992 ◽  
Vol 57 (6) ◽  
pp. 1423-1427 ◽  
Author(s):  
CONCEPCIÓN COLLAR ◽  
ARTURO F. MASCARÓS ◽  
CARMEN BENEDITO BARBER

2021 ◽  
Vol 15 ◽  
Author(s):  
Kexin Li ◽  
Yang Zheng ◽  
Xiaoming Wang

Hypoxia inducible factor (HIF) is one of the major transcription factors through which cells and tissues adapt to hypoxic-ischemic injury. However, the specific mechanism by which HIF regulates amino acid metabolism and its effect on neurons during hypoxic ischemia (HI) have remained unclear. This study analyzed the changes in cerebral metabolism of amino acids after HI by using 1H-MRS and investigated the relationship between the changes in cerebral metabolism of amino acids and HIF-1α as well as the potential effects on neurons. Newborn pigs were used as an HI model in this study. Twenty-eight newborn Yorkshire pigs (male, 1.0–1.5 kg) aged 3–5 days were selected and randomly divided into experimental groups tested at 0–2 h (n = 4), 2–6 h (n = 4), 6–12 h (n = 4), 12–24 h (n = 4), 24–48 h (n = 4), and 48–72 h (n = 4) after HI, and a control group (n = 4). After the modeling was completed, 1H-MRS imaging was conducted, followed by immunohistochemical staining of HIF-1α, NeuN, and doublecortin (DCX), and immunofluorescence of glutamic oxaloacetic transaminase (GOT)-1, GOT2, glutathione synthase (GS), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) in brain tissues. The expression of HIF-1α exhibited two increases after HI injury. The first time was opposite to the trends of change of GOT2, aspartic acid, and the number of neurons, while the second was consistent with these trends, suggesting that HIF-1α may have a two-way induction effect on neurons by regulating GOT2 after HI. HIF-1α was closely related to GCLM expression, and GSH level was correlated with the number of hippocampal neurons, indicating that HIF-1α may regulate GCLM to promote GSH synthesis and additionally play a neuroprotective role.


2020 ◽  
Author(s):  
Haihui Zhuang ◽  
Sira Karvinen ◽  
Xiaobo Zhang ◽  
Xiaowei Ojanen ◽  
Timo Törmakangas ◽  
...  

ABSTRACTAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging and their interaction on metabolism, we utilized rat models of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS) platform. Interaction of aerobic capacity and aging was studied via regression analysis. Our results showed at young age, metabolites linked to amino acid metabolism differed in serum and muscle with aerobic capacity, whereas no difference were observed in WAT. In aged animals, most prominent changes in metabolites occurred in WAT. Aerobic capacity and aging interactively affected seven metabolites linked to energy metabolism. Our results support previous findings that high aerobic capacity is associated with more efficient amino acid metabolism in muscle. While impaired branched chain amino acids (BCAAs) and fatty acid metabolism in the muscle may associate to the high risk of metabolic disorders and shorter lifespan previously observed in LCRs. The interactive effects of aging and aerobic capacity on energy metabolism-related metabolites were largely driven by HCRs, reflecting the importance of inherited aerobic capacity in the aging process. Our results highlight that dysfunctional mitochondrial β-oxidation in WAT may be one key mechanism related to aging.


Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 498-P
Author(s):  
MARK W. PATAKY ◽  
ARATHI PRABHA KUMAR ◽  
KATHERINE KLAUS ◽  
K. SREEKUMARAN NAIR

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