PubMed

Complete metabolic study by dibutyl phthalate degrading Pseudomonas sp. DNB-S1. Ecotoxicol Environ Saf. 2020 Mar 05;194:110378 Authors: Yu H, Wang L, Lin Y, Liu W, Tuyiringire D, Jiao Y, Zhang L, Meng Q, Zhang Y Abstract The primary purpose of this study was to systematically explore the complete metabolic pathway and tolerance mechanism of strain DNB-S1 to dibutyl phthalate (DBP), and the effect of DBP on energy metabolism of DNB-S1. Here, DNB-S1, a strain of Pseudomonas sp. that was highly effective in degrading DBP, was identified, and differentially expressed metabolites and metabolic networks of DBP were studied. The results showed that the differentially expressed metabolites were mainly aromatic compounds and lipid compounds, with only a few toxic intermediate metabolites. It speculated that phthalic acid, salicylic acid, 3-hydroxybenzoate acid, 3-Carboxy-cis, cis-muconate, fumarypyravate were intermediate metabolites of DBP. Their up-regulation indicated that there were two metabolic pathways in the degradation of DBP (protocatechuate pathway and gentisate pathway), which had been verified by peak changes at 290 nm, 320 nm, 330 nm, and 375 nm in the enzymatic method. Also, aspartate, GSH, and other metabolites were up-regulation, indicating that DNB-S1 had a high tolerance to DBP and maintained cell homeostasis, which was also one of the essential reasons to ensure the efficient degradation of DBP. Altogether, this study firstly proposed two pathways to degrade DBP and comprehensively explored the effect of DBP on the metabolic function of DNB-S1, which enriched the study of microbial metabolism of organic pollutants, and which provided a basis for the application of metabolomics. PMID: 32146194 [PubMed - as supplied by publisher]

Related Articles 1H-NMR metabolomics response to a realistic diet contamination with the mycotoxin deoxynivalenol: Effect of probiotics supplementation. Food Chem Toxicol. 2020 Mar 04;:111222 Authors: Alassane-Kpembi I, Canlet C, Tremblay-Franco M, Jourdan F, Chalzaviel M, Pinton P, Cossalter AM, Achard C, Castex M, Combes S, Bracarense APL, Oswald IP Abstract Low-level contamination of food and feed by deoxynivalenol (DON) is unavoidable. We investigated the effects of subclinical treatment with DON, and supplementation with probiotic yeast Saccharomyces cerevisiae boulardii I1079 as a preventive strategy in piglets. Thirty-six animals were randomly assigned to either a control diet, a diet contaminated with DON (3 mg/kg), a diet supplemented with yeast (4 × 109 CFU/kg), or a DON-contaminated diet supplemented with yeast, for four weeks. Plasma and tissue samples were collected for biochemical analysis, 1H-NMR untargeted metabolomics, and histology. DON induced no significant modifications in biochemical parameters. However, lesion scores were higher and metabolomics highlighted alterations of amino acid and 2-oxocarboxylic acid metabolism. Administering yeast affected aminoacyl-tRNA synthesis and amino acid and glycerophospholipid metabolism. Yeast supplementation of piglets exposed to DON prevented histological alterations, and partial least square discriminant analysis emphasised similarity between the metabolic profiles of their plasma and that of the control group. The effect on liver metabolome remained marginal, indicating that the toxicity of the mycotoxin was not eliminated. These findings show that the 1H-NMR metabolomics profile is a reliable biomarker to assess subclinical exposure to DON, and that supplementation with S. cerevisiae boulardii increases the resilience of piglets to this mycotoxin. PMID: 32145353 [PubMed - as supplied by publisher]

Related Articles Enhanced pseudotargeted analysis using a segment data dependent acquisition strategy by LC-MS/MS for a metabolomics study of liquiritin in the treatment of depression. J Sep Sci. 2020 Mar 07;: Authors: Yang J, Jin W, Liu D, Zhong Q, Zhou T Abstract An enhanced pseudotargeted method using a segment data dependent acquisition mode based on ultra-high performance liquid chromatography-mass spectrometry was developed. This segment data dependent acquisition-based pseudotargeted method could improve the detection of co-eluted ions and extend the coverage of analytes. A set of 502 multiple reaction monitoring channels were obtained by this segment strategy, which was twice the number created by the traditional data dependent acquisition mode. Compared with the untargeted method, the pseudotargeted profiling demonstrated higher sensitivity and higher precision. More than 90% of the metabolites detected by the enhanced pseudotargeted method had RSDs less than 15%. The segment data dependent acquisition-based pseudotargeted method was successfully applied to the metabolomics study of the depressed rats with the treatment of liquiritin. Forty-seven differential metabolites were screened and five metabolic pathways were found to be relate to depression including retinol metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, terpenoid backbone biosynthesis and lysine degradation. The segment data dependent acquisition-based pseudotargeted method widened the coverage of metabolites with good sensitivity and precision, which exhibited great potential in the discovery of differential metabolites in metabolomics studies. This article is protected by copyright. All rights reserved. PMID: 32144949 [PubMed - as supplied by publisher]

Related Articles Current status of retention time prediction in metabolite identification. J Sep Sci. 2020 Mar 07;: Authors: Witting M, Böcker S Abstract Metabolite identification is a crucial step in non-targeted metabolomics, but also represents one of its current bottlenecks. Accurate identifications are required for correct biological interpretation. To date, annotation and identification are usually based on the use of accurate mass search or tandem MS analysis, but neglect orthogonal information such as retention times obtained by chromatographic separation. While several tools are available for the analysis and prediction of tandem MS data, prediction of retention times for metabolite identification are not widespread. Here, we review the current state of retention time prediction in liquid chromatography-mass spectrometry-based metabolomics, with a focus on publications published after 2010. This article is protected by copyright. All rights reserved. PMID: 32144942 [PubMed - as supplied by publisher]

Related Articles A role for metabolomics in the anti-doping toolbox? Drug Test Anal. 2020 Mar 06;: Authors: Narduzzi L, Dervilly G, Audran M, Le Bizec B, Buisson C Abstract The evidence of continuous rise of novel doping agents and novel doping strategies calls for the development of more accurate multi-target screening methods. Direct multi-target screening approaches are restricted to the targeted substances and their turnover. The development of effective "indirect" screening methods requires a priori deep-understanding of the substance metabolism. The biological passport has been demonstrated to be very effective, but it is limited to about 20 indirect parameters. The standard anti-doping analytical methods are hence targeted and does not aim to directly identify unknown substances. Also, the detection of doping agents is limited by the substances excretion. We propose to consider metabolomics for screening of abuse of performance enhancing hormones by athletes, with the basis on the following pieces of evidence: 1) Hormones have a strong influence on human metabolism, changing several parameters in many tissues, organs, and bio-fluids. 2) Metabolomics has been demonstrated to be a very accurate tool to depict the metabolic status of several organisms, tissues and for several human diseases, including hormonal deficiencies. 3) Metabolomics has been demonstrated to be able to distinguish hormone-treated animals from controls in many species, without the need of a priori knowledge of the metabolism for the specific substance. The literature shows that metabolomics could be an appropriate tool to detect hormonal abuse, keeping in mind the strength and the limitation of such an approach. PMID: 32144900 [PubMed - as supplied by publisher]

Related Articles A high-throughput platform for detailed lipidomic analysis of a range of mouse and human tissues. Anal Bioanal Chem. 2020 Mar 07;: Authors: Furse S, Fernandez-Twinn DS, Jenkins B, Meek CL, Williams HEL, Smith GCS, Charnock-Jones DS, Ozanne SE, Koulman A Abstract Lipidomics is of increasing interest in studies of biological systems. However, high-throughput data collection and processing remains non-trivial, making assessment of phenotypes difficult. We describe a platform for surveying the lipid fraction for a range of tissues. These techniques are demonstrated on a set of seven different tissues (serum, brain, heart, kidney, adipose, liver, and vastus lateralis muscle) from post-weaning mouse dams that were either obese (> 12 g fat mass) or lean (<5 g fat mass). This showed that the lipid metabolism in some tissues is affected more by obesity than others. Analysis of human serum (healthy non-pregnant women and pregnant women at 28 weeks' gestation) showed that the abundance of several phospholipids differed between groups. Human placenta from mothers with high and low BMI showed that lean placentae contain less polyunsaturated lipid. This platform offers a way to map lipid metabolism with immediate application in metabolic research and elsewhere. Graphical abstract. PMID: 32144454 [PubMed - as supplied by publisher]

Related Articles Oxygen consumption rate of Caenorhabditis elegans as a high-throughput endpoint of toxicity testing using the Seahorse XFe96 Extracellular Flux Analyzer. Sci Rep. 2020 Mar 06;10(1):4239 Authors: Preez GD, Fourie H, Daneel M, Miller H, Höss S, Ricci C, Engelbrecht G, Zouhar M, Wepener V Abstract Caenorhabditis elegans presents functioning, biologically relevant phenotypes and is frequently used as a bioindicator of toxicity. However, most C. elegans in vivo effect-assessment methods are laborious and time consuming. Therefore, we developed a novel method to measure the oxygen consumption rate of C. elegans as a sublethal endpoint of toxicity. This protocol was tested by exposing 50 larval stage one C. elegans individuals for 48 h (at 20 °C) to different concentrations of two toxicants i.e. benzylcetyldimethylammonium chloride (BAC-C16) and cadmium (Cd). Following exposures, the oxygen consumption rate of the C. elegans individuals were measured using the high-throughput functionality of the Seahorse XFe96 Extracellular Flux Analyzer. Dose-response curves for BAC-C16 (R2 = 0.93; P = 0.001) and Cd (R2 = 0.98; P = 0.001) were created. Furthermore, a strong, positive correlation was evidenced between C. elegans oxygen consumption rate and a commonly used, ecologically relevant endpoint of toxicity (growth inhibition) for BAC-C16 (R2 = 0.93; P = 0.0001) and Cd (R2 = 0.91; P = 0.0001). The data presented in this study show that C. elegans oxygen consumption rate can be used as a promising functional measurement of toxicity. PMID: 32144330 [PubMed - as supplied by publisher]

Related Articles Differential metabolic profile associated with the condition of normoalbuminuria in the hypertensive population. Nefrologia. 2020 Mar 03;: Authors: Santiago-Hernandez A, Martinez PJ, Martin-Lorenzo M, Ruiz-Hurtado G, G Barderas M, Segura J, Ruilope LM, Alvarez-Llamas G Abstract BACKGROUND AND AIM: Albuminuria is an indicator of sub-clinical organ damage and a marker of cardiovascular risk and renal disease. A percentage of hypertensive patients develop albuminuria despite being under chronic suppression of the renin-angiotensin system (RAS). We previously identified urinary metabolites associated with the development of albuminuria. In this study, we searched for metabolic alterations which reflect different levels within the condition of normoalbuminuria. PATIENTS, MATERIALS AND METHODS: Urine from 48 hypertensive patients under chronic RAS suppression was analysed. They were classified according to the albumin/creatinine ratio (ACR) into 3groups: Normoalbuminuria (<10mg/g); high-normal (10-30mg/g in men, or 20-40mg/g in women); and moderately high albuminuria (microalbuminuria, 30-200mg/g or 40-300mg/g, respectively). The metabolome was analysed by mass spectrometry and a correlation analysis was performed between altered metabolite levels and ACR. RESULTS: Oxaloacetate, 3-ureidopropionate, guanidoacetate and malate show significant variation between the normo and micro groups. Additionally, these metabolites are able to differentiate between patients in the normo and high-normal range. A significant correlation between metabolites and ACR was found. Observed variations point to alterations in the energy metabolism already in patients with albuminuria in the high-normal range. CONCLUSIONS: The association between the molecular panel consisting of 3-ureidopropionate, oxaloacetate, malate and guanidoacetate and different levels of albuminuria is confirmed. A metabolic fingerprint was also identified showing variations within the condition of normoalbuminuria allowing an earlier molecular stratification of patients. PMID: 32144010 [PubMed - as supplied by publisher]

50 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/03/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

50 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/03/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/03/06PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

DNA barcoding for the identification of mold species in bakery plants and products. Food Chem. 2020 Feb 26;318:126501 Authors: Ollinger N, Lasinger V, Probst C, Pitsch J, Sulyok M, Krska R, Weghuber J Abstract Mold identification at the species level in environmental samples is a major challenge. Molecular techniques have been widely used for fungal classification, but as most primers are genus-specific, it is laborious to identify unknown samples. In this study, a PCR-based method for the identification of mold at the species level was developed. Therefore, common sequencing primers and combinations of them, targeting specific DNA regions, were tested. Here we present a combination of eight primer pairs to identify mold within a single PCR run. The approach correctly identified mold of unknown species from samples taken at a local bakery, including Penicillium chrysogenum, Penicillium citrinum, Cladosporium sphaerospermum, Paecilomyces formosus, Rhizopus oryzae and Aspergillus niger. Results obtained from the PCR method were successfully validated by chromatographic mycotoxin and microscopy analysis. Findings highlight DNA barcoding as an appropriate tool for mold identification; however, its efficacy is essentially dependent on DNA quality and primer selection. PMID: 32131042 [PubMed - as supplied by publisher]

Exploring Cancer Metabolism: Applications of Metabolomics and Metabolic Phenotyping in Cancer Research and Diagnostics. Adv Exp Med Biol. 2020;1219:367-385 Authors: Graça G, Lau CE, Gonçalves LG Abstract Altered metabolism is one of the key hallmarks of cancer. The development of sensitive, reproducible and robust bioanalytical tools such as Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry techniques offers numerous opportunities for cancer metabolism research, and provides additional and exciting avenues in cancer diagnosis, prognosis and for the development of more effective and personalized treatments. In this chapter, we introduce the current state of the art of metabolomics and metabolic phenotyping approaches in cancer research and clinical diagnostics. PMID: 32130709 [PubMed - as supplied by publisher]

Ovarian Cancer Biomarkers: Moving Forward in Early Detection. Adv Exp Med Biol. 2020;1219:355-363 Authors: Bonifácio VDB Abstract Ovarian cancer is a silent cancer which rate survival mainly relays in early stage detection. The discovery of reliable ovarian cancer biomarkers plays a crucial role in the disease management and strongly impact in patient's prognosis and survival. Although having many limitations CA125 is a classical ovarian cancer biomarker, but current research using proteomic or metabolomic methodologies struggles to find alternative biomarkers, using non-invasive our relatively non-invasive sources such as urine, serum, plasma, tissue, ascites or exosomes. Metabolism and metabolites are key players in cancer biology and its importance in biomarkers discovery cannot be neglected. In this chapter we overview the state of art and the challenges facing the use and discovery of biomarkers and focus on ovarian cancer early detection. PMID: 32130708 [PubMed - as supplied by publisher]

Serum amino acid metabolic profiles of ankylosing spondylitis by targeted metabolomics analysis. Clin Rheumatol. 2020 Mar 04;: Authors: Zhou Y, Zhang X, Chen R, Han S, Liu Y, Liu X, Gao M, Yang C, Lu D, Sun B, Chen H Abstract BACKGROUND: Ankylosing spondylitis (AS) is a common chronic inflammatory arthritis, causing lasting back pain with progressive loss of spinal mobility. However, the exact pathogenesis of AS remains unclear. We aim to use the metabolomics analysis to characterize the metabolic profile of AS, in order to better understand the pathogenesis of AS and monitor disease activity and progression. METHODS: The ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS) was used for investigating the serum amino acid metabolomic profiling of 30 AS patients, in comparison with 32 rheumatoid arthritis (RA) patients and 30 healthy controls, combined with multivariate statistical analysis. Metabolite association analysis with disease activity was performed using generalized linear regression. The metabolic pathway analysis for the important metabolites was performed using MetPA and the metabolic network was constructed. RESULTS: A total of 29 amino acids and biogenic amines were detected in all participants by UPLC-TQ-MS. It showed significant amino acid differences between the AS/RA patients and control subjects. Additionally, 4-hydroxy-L-proline, alanine, γ-aminobutyric acid, glutamine, and taurine were identified as candidate markers shared by AS/RA groups. Specifically, lysine, proline, serine, and alanine were found correlated with disease activity of AS. Furthermore, the most significant metabolic pathway identified were alanine, aspartate, and glutamate metabolism, arginine and proline metabolism, aminoacyl tRNA biosynthesis and glycine, serine, and threonine metabolism. CONCLUSIONS: These preliminary results demonstrate that UPLC-TQ-MS analysis method is a powerful tool to identify metabolite profiles of AS. Research in identified disease activity-associated metabolites and biological pathways may provide assistance for clinical diagnosis and pathological mechanism of AS.Key Points• There are perturbations of serum amino acid metabolism in AS, compared with RA and healthy controls, determined by UPLC-TQ-MS.• Metabolomics pathway is used to analysis for the differential metabolites of AS.• The altered serum amino acid could monitor disease activity of AS. PMID: 32130577 [PubMed - as supplied by publisher]

Preparative supercritical fluid chromatography for lipid class fractionation-a novel strategy in high-resolution mass spectrometry based lipidomics. Anal Bioanal Chem. 2020 Mar 04;: Authors: Schoeny H, Rampler E, Hermann G, Grienke U, Rollinger JM, Koellensperger G Abstract In this work, a lipidomics workflow based on offline semi-preparative lipid class-specific fractionation by supercritical fluid chromatography (SFC) followed by high-resolution mass spectrometry was introduced. The powerful SFC approach offered separation of a wide polarity range for lipids, enabled enrichment (up to 3 orders of magnitude) of lipids, selective fractionation of 14 lipid classes/subclasses, and increased dynamic range enabling in-depth characterization. A significantly increased coverage of low abundant lipids improving lipid identification by numbers and degree (species and molecular level) was obtained in Pichia pastoris when comparing high-resolution mass spectrometry based lipidomics with and without prior fractionation. Proof-of-principle experiments using a standard reference material (SRM 1950, NIST) for human plasma showed that the proposed strategy enabled quantitative lipidomics. Indeed, for 70 lipids, the consensus values available for this sample could be met. Thus, the novel workflow is ideally suited for lipid class-specific purification/isolation from milligram amounts of sample while not compromising on omics type of analysis (identification and quantification). Finally, compared with established fractionation/pre-concentration approaches, semi-preparative SFC is superior in terms of versatility, as it involved only volatile modifiers and salt additives facilitating any follow-up use such as qualitative or quantitate analysis or further purification down to the single lipid species level. Graphical Abstract. PMID: 32130438 [PubMed - as supplied by publisher]

Potent USP10/13 antagonist spautin-1 suppresses melanoma growth via ROS-mediated DNA damage and exhibits synergy with cisplatin. J Cell Mol Med. 2020 Mar 04;: Authors: Guo J, Zhang J, Liang L, Liu N, Qi M, Zhao S, Su J, Liu J, Peng C, Chen X, Liu H Abstract Malignant melanoma is one of the most invasive tumours. However, effective therapeutic strategies are limited, and overall survival rates remain low. By utilizing transcriptomic profiling, tissue array and molecular biology, we revealed that two key ubiquitin-specific proteases (USPs), ubiquitin-specific peptidase10 (USP10) and ubiquitin-specific peptidase10 (USP13), were significantly elevated in melanoma at the mRNA and protein levels. Spautin-1 has been reported as a USP10 and USP13 antagonist, and we demonstrated that spautin-1 has potent anti-tumour effects as reflected by MTS and the colony formation assays in various melanoma cell lines without cytotoxic effects in HaCaT and JB6 cell lines. Mechanistically, we identified apoptosis and ROS-mediated DNA damage as critical mechanisms underlying the spautin-1-mediated anti-tumour effect by utilizing transcriptomics, qRT-PCR validation, flow cytometry, Western blotting and immunofluorescence staining. Importantly, by screening spautin-1 with targeted or chemotherapeutic drugs, we showed that spautin-1 exhibited synergy with cisplatin in the treatment of melanoma. Pre-clinically, we demonstrated that spautin-1 significantly attenuated tumour growth in a cell line-derived xenograft mouse model, and its anti-tumour effect was further enhanced by cotreatment with cisplatin. Taken together, our study revealed a novel molecular mechanism of spautin-1 effecting in melanoma and identified a potential therapeutic strategy in treatment of melanoma patients. PMID: 32129945 [PubMed - as supplied by publisher]

Simultaneous increases in the levels of compatible solutes by cost-effective cultivation of Synechocystis sp. PCC 6803. Biotechnol Bioeng. 2020 Mar 04;: Authors: Iijima H, Watanabe A, Sukigara H, Shirai T, Kondo A, Osanai T Abstract Synechocystis sp. PCC 6803, a cyanobacterium widely used for basic research, is often cultivated in a synthetic medium, BG-11, in the presence of 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid (HEPES) or 2-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]amino]ethanesulfonic acid buffer. Owing to the high cost of HEPES buffer (96.9% of the total cost of BG-11 medium), the biotechnological application of BG-11 is limited. In this study, we cultured Synechocystis sp. PCC 6803 cells in BG-11 medium without HEPES buffer and examined the effects on the primary metabolism. Synechocystis sp. PCC 6803 cells could grow in BG-11 medium without HEPES buffer after adjusting for nitrogen sources and light intensity; the production rate reached 0.54 g cell dry weight/L/day, exceeding that of commercial cyanobacteria and Synechocystis sp. PCC 6803 cells cultivated under other conditions. The exclusion of HEPES buffer markedly altered the metabolites in the central carbon metabolism; particularly, the levels of compatible solutes, such as sucrose, glucosylglycerol, and glutamate were increased. Although the accumulation of sucrose and glucosylglycerol under high salt conditions is antagonistic to each other, these metabolites accumulated simultaneously in cells grown in the cost-effective medium. Because these metabolites are used in industrial feedstocks, our results reveal the importance of medium composition for the production of metabolites using cyanobacteria. This article is protected by copyright. All rights reserved. PMID: 32129469 [PubMed - as supplied by publisher]

Intact NMR spectroscopy: slow high-resolution magic angle spinning chemical shift imaging. Analyst. 2020 Mar 04;: Authors: Lucas-Torres C, Wong A Abstract High-Resolution Magic-Angle Spinning Chemical Shift Imaging (HR-MAS CSI) has recently been explored for nuclear magnetic resonance (NMR) metabolomics and shows considerable promise in organism research. This is due to its ability to offer a supplemental dimension - spatial metabolic distribution - for profiling. However, HR-MAS CSI suffers from the large centrifugal stress exerted on the sample, which inevitably hinders the metabolic assessment. Herein, a slow sample spinning strategy was implemented and evaluated. The results demonstrate its potential as a highly informative profiling approach for intact specimens, with high quality data and feasibility. PMID: 32129382 [PubMed - as supplied by publisher]

Rosmarinic acid alleviates ethanol-induced lipid accumulation by repressing fatty acid biosynthesis. Food Funct. 2020 Mar 04;: Authors: Guo C, Shangguan Y, Zhang M, Ruan Y, Xue G, Ma J, Yang J, Qiu L Abstract Recent studies have demonstrated that rosmarinic acid is a valuable natural product for treatment of alcoholic liver disease. However, the mechanisms whereby rosmarinic acid improves alcoholic liver disease remain unclear. Here we performed experiments using a non-transformed mouse hepatocyte cell line (AML12). Oil-red O staining demonstrated that rosmarinic acid reduced ethanol-induced lipid accumulation. It was shown that rosmarinic acid prevented ethanol-induced elevation of the malondialdehyde level. We also found that rosmarinic acid inhibited ethanol-induced mRNA expression of tumor necrosis factor-α and interleukin 6. Metabolomics analysis revealed that rosmarinic acid ameliorated ethanol-induced fatty acid biosynthesis in the cytoplasm. In addition, palmitic acid was a candidate biomarker in cells exposed to ethanol or ethanol plus rosmarinic acid. Rosmarinic acid prevented the ethanol-induced increase in sorbitol that is a component of the polyol pathway. Moreover, we confirmed that rosmarinic acid attenuated ethanol-induced mRNA expression of fatty acid synthase, probably by modulating the AMPK/SREBP-1c pathway. Furthermore, rosmarinic acid prevented the ethanol-induced decrease in eight metabolites that are involved in mitochondrial metabolism, including glycine and succinic acid which are the components of carnitine synthesis. These results provide a crucial insight into the molecular mechanism of rosmarinic acid in alleviating ethanol-induced injury. PMID: 32129352 [PubMed - as supplied by publisher]