MultiQuant 3.0.2 software was used to extract the original MRM data of MT1000 KIT metabolites and obtain the peak area of each metabolite for quantification from different samples.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - alternating - reverse-phase"],"chromatography_protocol":["The LC/MS portion of the platform was based on a Shimadzu Nexera X2 LC-30AD system equipped with an ACQUITY UPLC HSS T3 column (1.7 μm, 2.1 mm×100 mm, Wasters) and a triple quadruple mass spectrometer (5500 QTRAP, AB SCIEX). Metabolites were detected in electrospray negative-ionization and positive-ionization mode. The 2 μL samples were injected sequentially with LC autosampler. The ACQUITY UPLC HSS T3 column (1.7 μm, 2.1 mm×100 mm, Wasters) was heated to 40 °C under a flow rate of 200 μL/min. A gradient was used to separate the compounds consisted of 0.1% Formic acid aqueous solution (solvent A) and 100% acetonitrile (solvent B). The gradient started at 100% solvent A for 2.5 min and increasing linearly to 70% solvent A over 9 min, and then increasing linearly to 0% solvent A over 1 min following with a 5.4 min hold before returning the starting mixture during 0.1min and re-equilibrating for 2.5 min. QC samples were injected every several samples during acquisition to monitor the reproducibility of the test.
"],"publication":["Podophyllotoxin-induced nephrotoxicity via the microbiota-gut-kidney axis in SD rats based on the toxicological evidence chain (TEC) concept.","targeted metabolomics of rat's kidney."],"submitter_affiliation":["The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology"],"submitter_name":["Xuejiao Li"],"organism_part":["kidney"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["The metabolites were extracted from kidney tissues with 1 mL precooled methanol/acetonitrile/water (v/v, 2:2:1) under sonication for 1 h in ice baths. The mixture was incubated at -20 °C for 1 h followed by centrifugation at 16,000 g, 4 °C for 20 min, and then transferred to the sampling vial for LC-MS analysis.
"],"organism":["Rattus norvegicus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS14869"],"author":["Xuejiao Li. The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology. white_snow1987@163.com.","Chuanxin Liu. The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology. 9906194@haust.edu.cn."],"data_transformation_protocol":["The discriminating metabolites were obtained using a statistically significant threshold of variable influence on projection (VIP) values obtained from the OPLS-DA model and two-tailed Student’s t test (p value) on peak area of each metabolite for two groups comparison. The p value was calculated by one-way analysis of variance (ANOVA) for multiple groups analysis. Metabolites with VIP> 1 and p value< 0.05 were considered to be statistically significant. The significantly differential metabolites were used to perform cluster analyses with R package.
"],"study_factor":["Treatment","Dose"],"submitter_email":["white_snow1987@163.com"],"sample_collection_protocol":["Euthanasia was carried out after anesthesia induced with 1.25% tribromoethanol, and samples of blood, kidney, colon106
tissues, and colonic feces were taken for further analysis, such as organ index assessment,107
biochemical tests, histological inspection, and multi-omics research
"],"omics_type":["Metabolomics"],"study_design":["kidney","podophyllotoxin","Metabolomics","Thermo Scientific Q Exactive","Rattus norvegicus","Shimadzu Nexera UHPLC system","experimental blank","targeted metabolite profiling","semi-targeted analysis"],"curator_keywords":["kidney","podophyllotoxin","Metabolomics","Thermo Scientific Q Exactive","Rattus norvegicus","Shimadzu Nexera UHPLC system","experimental blank","targeted metabolite profiling","semi-targeted analysis"],"mass_spectrometry_protocol":["Widely targeted metabolites were quantified using multiple-reaction monitoring mode set up as previous report described (Cao, G., et al. 2020; Zheng, F., et al. 2020). All transitions from large-scale metabolites (MT1000 Kit developed by Shanghai BioProfile) were detected with optimized decluttering potential and collision energy. The MS conditions were set as follows: negative-ionization mode: Source Temperature 550℃, Ion Source Gas1 (GAS1): 40, Ion Source Gas2 (GAS2): 50, Curtain Gas (CUR): 35, Ion Spray Voltage Floating (ISVF) :-4500V; positive-ionization mode: Source Temperature 550℃, Ion Source Gas1 (GAS1): 40, Ion Source Gas2 (GAS2): 50, Curtain Gas (CUR): 35, Ion Spray Voltage Floating (ISVF) :5500V.
"],"metabolite_name":["DEOXYCARNITINE","beta-Hydroxymyristic acid","dGDP","PS(18:0/18:0)","DL-2-Aminooctanoic acid","Phenylacetylglutamine","LPE(18:2)","Riboflavin","Docosatetraenoic acid","Folic acid","Butyric acid","Deoxyinosine","Ectoine","Ketoleucine","CEA","O-Succinyl-L-homoserine","D-glucosamine 1-phosphate","Flavone","O-Acetyl-L-serine","Nicotinic acid adenine dinucleotide","LPE(18:3)","Biotin","Cytidine diphosphate ethanolamine","Citrulline","CEL","GMP","alpha-Muricholic acid","1-Methylxanthine","D-Glucuronic acid","Flavin mononucleotide","Dimethyl-L-arginine","Hyocholic acid","SM 40:4;3","3-Hydroxyanthranilic acid","Deoxycorticosterone","Hexanoylcarnitine","Alpha-N-Phenylacetyl-L-glutamine","histamine","Hexose Pool","PE(P-16:0/22:5)","Glycine","Estradiol","L-Pipecolic acid","LPE(18:0)","Hordenine","Mevalonic acid","Arginine","Imidazole","13S-hydroxyoctadecadienoic acid","DG(16:0/22:5)","SM 42:0;2","2'-Deoxycytidine diphosphate","D-Glucose 1-phosphate","THP","PG(18:0/18:2)","SM 32:2;3","PC(18:1/18:3)","PA(16:0/16:0)","12 Dehydrocholic Acid sulfate","N6-acetyl lysine","4-Methyl-2-oxovaleric acid","FA(18:0)","Pseudouridine","LPE(18:1)","2-Ketoglutaric acid","Coenzyme Q(9)","14,15-DHET","Oleamide","3-phosphoglycerate","Tiglylcarnitine","DG(16:0/22:6)","N-Acetyl-5-hydroxytryptamine","N-Acetylneuraminic acid","Thiazolidine-4-carboxylic acid","4-Pyridoxic acid","Pantothenic acid","Vitamin D3","Glycerol 3-phosphate","DG(16:0/20:4)","Guanosine","SM 34:1;3","Citrate","beta-D-Glucosamine","FA(18:1)","Glyceraldehyde 3-phosphate","Xanthurenic acid","ADP","D-Glucosamine 6-phosphate","Shikimic acid","DG(18:1/20:5)","Monoisobutyl phthalate","Shikimate-3-phosphate","Glyceric acid","cis-aconitic acid","Gamma-glutamyl-Alanine","1alpha,25-Dihydroxyvitamin D3","Alanylphenylalanine","FA(18:2)","Phenethylacetate","Carnitine-C6DC","Prostaglandin D2","1-Cinnamoylpyrrolidine","DG(18:1/20:4)","Methylguanidine","Pyridine","Uridine 5-monophosphate","4-Hydroxyquinoline","L-Thyronine","Pyrophosphate","Uridine","L-Homocysteic acid","Androstenedione","Ornithine","D-Gluconic acid","Retinal","SM 40:2;3","Vitamin B1","3-Ureidopropanoate","24-OH cholesterol","Isovalerylcarnitine","SM 34:0;3","2-Hydroxyadenine","Indole","Serine","Proline","FA(18:3)","5-Hydroxy-6,8,11,14,17-eicosapentaenoic acid","Lactamide","3,7-Dimethyluric acid","L-2-Hydroxygluterate","Tridecanoic acid","7-ketocholesterol","N-alpha-Acetylarginine","2-Hydroxybenzoic acid","Malonyl-CoA","LPC(18:1)","Valylphenylalanine","Adenosine","L-Ascorbic acid","PS(18:0/18:1)","dIMP","N-Acetyltryptophan","Uric acid","NAD","DG(18:1/20:2)","Pimelylcarnitine","11,12-DiHETrE","L-O-Phosphoserine","TMP","D-Erythrose 4-phosphate","N-Acetyl-D-glucosamine 1-phosphate","tetranor-Prostaglandin E Metabolit","S-Carboxymethyl-L-cysteine","gamma-L-Glutamyl-L-valine","Hypotaurine","SM 40:1;3","SM 40:1;2","Cyclic adenosine monophosphate","SM 40:1;4","Benzoic acid","Melatonin","5-Methylcytosine","2'-Deoxyguanosine 5'-monophosphate","Ala-Leu","Mannose","Glucose","gamma-Glutamyltyrosine","Glycylproline","L-histidinol","2-Pyrocatechuic acid","PE(18:0/14:0)","CMA","Spermidine","FA(14:0)","N-Acetyl-L-tyrosine","SM 42:3;3","D-Fructose 1,6-bisphosphate","Carnitine-C16:1","gamma-Glutamylleucine","Taurocholic acid","FA(24:4)","S-Sulfo-L-cysteine","CML","2-Isopropylmalic acid","Threonine","Taurodeoxycholic acid Pool","5-Aminolevulinate","PI(16:0/16:1)","LPE(16:1)","Carnitine-C4DC","Urocanic acid","Valeric acid","Abietic acid","Lysine","L-Cystathionine","4-Aminobenzoic acid","Methylsuccinic Acid","N-Fructosyl tyrosine","Hydroxyproline","L-Abrine","SM 34:2;3","Guanine","Carnitine-C12","5'-Methylthioadenosine","Carnitine-C10","4-Nitrophenol","1-Methylnicotinamide","NADH","Carnitine-C16","Carnitine-C14","1,5-anhydroglucitol","UDPglucose","Carnitine-C18","NADP","Acamprosate","Xanthosine","Aspartate","N-Carbamoyl-L-aspartate","Pyridoxine","3-Methyl-2-oxovaleric acid","Carnitine-C5DC","Uridine 5'-monophosphate","Uridine diphosphate-n-acetyl-D-glucosamine","N-Fructosyl phenylalanine","SM 44:0;3","Chenodeoxycholic Acid sulfate","PA(16:1/18:1)","5-Aminopentanoic acid","3-Hydroxyhexanoylcarnitine","1-Methyladenine","2-Phenylacetamide","Valine","Suberic Acid","Arachidonyl carnitine","P-Toluenesulfonic acid","Hexaethylene glycol","N6-lactoyl","Succinyl-CoA","L-beta-Homotyrosine","Phosphotyrosine","Taurochenodeoxycholic Acid","Bilirubin","BMP(18:1/16:1)","5-Methyltetrahydrofolate","Glycocholic acid","Nicotinamide ribotide","Tauro-alpha/beta/omega muricholic acid","BMP(18:1/16:0)","Betaine","Carnitine-C14:1","Indole-3-carboxaldehyde","Carnitine-C10 OH","SM 42:1;2","3-methoxytyramine","Flavin adenine dinucleotide","Deoxyribose phosphate","AMP","PC(18:1/18:1)","6-Hydroxynicotinic acid","Cinnamoylglycine","N6-formyl","Anandamide","Taurohyocholic acid","Dehydroascorbic acid","N-Acetyl-L-aspartic acid","3alpha,12alpha, 23-Nordeoxycholic Acid sulfate","DG(18:1/18:1)","8-hydroxyguanosine","N-methylphenethylamine","Pyroglutamyl-Isoleucine","LPC(16:0)","SM 36:0;2","3alpha-Hydroxy-12 Ketolithocholic Acid sulfate","Adenosine 5'-phosphosulfate","p-Aminohippuric acid","23-Nordeoxycholic acid","1-Methylhistidine","Gamma-glutamyl-Cysteine","FA(16:0)","SM 42:2;3","7-Ketolithocholic acid","L-Lactate","Indolelactate","Thymine","FA(16:2)","Carnitine-C3DC","1-Methyladenosine","Dodecylbenzenesulfonic acid","7-methylguanine","FA(16:1)","Alpha-D-Ribose 5-phosphate","4-Hydroxyphenylacetic acid","Sarcosine","Glycodehydrocholic acid","Taurine","FA(22:3)","Allantoin","3,4-Dihydroxyphenylacetic acid","Glucaric acid","O-Phosphoethanolamine","DG(18:0/22:6)","Cholic acid sulfate","L-Homoserine","Dephosphocoenzyme A","L-Threonine","Guanosine diphosphate","Phosphoenolpyruvate","Adenosine phosphosulfate","Kynurenic acid","Agmatine","Hexose Disaccharide Monophosphate Pool","Pyridoxal","FA(22:2)","Pyrraline","Carnitine-C0","Methionine","5-Hydroxyindole-3-acetic acid","Estriol(E3)","N-Acetyl-D-glucosamine","Apocholic acid","DG(16:1/20:4)","Oxaloacetic acid","Carnitine-C5OH","SM 36:2;3","dTMP","2-Naphthalenesulfonic acid","PE(18:1/16:1)","SM 30:1;4","cAMP","UDP-glucuronate","Cystine","N-Acetylglutamine","LPE(22:6)","Orotidine monophosphate","FA(12:0)","Lithocholenic acid sulfate","3-methylphenylacetic acid","Inosine 5'-monophosphate","Pentadecanoic acid","Myo-Inositol","Phenylalanine","PG(18:1/18:1)","Serotonin","(5-L-Glutamyl)-L-glutamine","Isoleucylisoleucine","Phenylacetylglycine","Epiandrosterone","Thiamin pyrophosphate","Deoxycytidine monophosphate","Leucylproline","SM 36:3;3","gamma-Glutamyl-L-methionine","Carnitine-C16OH","ATP","Aconitate","Eicosapentaenoic acid","Gamma-Aminobutyric acid","Carnitine-C18:2","L-Kynurenine","Creatine","7-methylguanosine","Sphingosine 1-phosphate","Carnitine-C8:1","Threonylleucine","Caprylic acid","Phytosphingosine","Octulose-monophosphate","N6-glycerinyl","2-Acetylpyrazine","Cytosine","Glycodeoxycholic acid sulfate","Carnitine-C18:1","LPE(22:4)","beta-Muricholic acid","D-Glucose 6-phosphate","PE(18:2/18:2)","Tyrosine","FA(22:6)","Homoarginine","N6-oxalyl","N2,N2-Dimethylguanosine","12-Ketolithocholic acid","L-beta-Homothreonine","Quinolin-2,8-diol","11-Hydroxyeicosatetraenoic acid","SM 44:1;3","2-keto-D-Gluconic acid","LPE(22:5)","SM 44:1;2","3-Indolepropionic acid","Sepiapterin","Succinic acid","Hypoxanthine","N6-methyladenosine","8(R)-hydroxy- eicosatetraenoic acid","Phenyllactic acid","L-Malate","Adipic acid","2,4-Dinitrophenol","Gluconolactone","Glyco-ursocholanic Acid","Phenylalanylisoleucine","Guanidinoacetic acid","3-FORMYLINDOLE","FA(24:3)","Hippuric acid","Desmosterol","Deoxythymidine diphosphate","N-Acetylaspartylglutamate","Sedoheptulose monophosphate","2-Arachidonoylglycerol","DG(14:0/18:2)","N6-threonyl","D-Ala-D-ala","SM 38:1;2","N,N-Dimethylaniline","Homovanillic acid","Resveratrol","Carnitine-C2","Carnitine-C4","Carnitine-C16:1OH","Carnitine-C3","Carnitine-C6","Carnitine-C5","Carnitine-C8","Deoxyuridine monophosphate","5-Amino-4-carbamoylimidazole","FA(24:2)","Pyruvate","Hydroxycholesterol species","Fructose","Nicotinuric acid","Carnitine-C4OH","Heptadecanoic acid","Citraconic acid","Inosine","Norepinephrine","Purine","PC(14:0/18:1)","Dimethylglycine","Taurocholic acid-3-O-sulfate","Serylleucine","Glutamine","PE(18:1/18:1)","N-Acetyl-L-phenylalanine","4-Hydroxyphenylpyruvate","FA(20:1)","Dihydroxyacetone phosphate","2'-O-methyladenosine","Cholic acid","N-Acetylmethionine","11,12-Epoxyeicosatrienoic acid","SM 38:2;3","2-Deoxy-D-glucose","Histidine","20-Hydroxyeicosatetraenoic acid","Anserine","Ureidosuccinic acid","Saccharopine","Na-Methyl-L-ornithine monohydrochloride","3-Methylhistidine","MODIC","Caffeine","4-Hydroxybenzoylcholine","(S)-12-Hydroxyeicosatetraenoic acid","SM 40:0;2","3-Hydroxybenzaldehyde","Allocholic acid","FA(20:0)","N-acetylserine","Vanillylmandelic acid","Farnesyl diphosphate","5-hydroxyeicosatatraeniocacid","3, 5-Tetradecadiencarnitine","Sebacic acid","beta-Sitosterol","Quercetin","N4-Acetylcytidine","N-Acetylhistamine","SM 40:0;4","Glycerophosphocholine","Ergothioneine","DhCer d18:0/26:0","FA(20:3)","PE(18:1/18:3)","NG,NG-Dimethyl-L-arginine","Leucyl-leucine","S-Methyl-L-cysteine","N-Acetylornithine","Targinine","Cytidine diphosphate choline","SM 38:3;3","Pyroglutamic acid","Cytidine triphosphate","N-Methylglutamic acid","Betaine aldehyde","LPE(20:4)","Deoxyguanosine triphosphate","8,9-DiHETrE","Salicylic acid","Alanine","L-Argininosuccinic acid","FA(20:2)","N-Acetylputrescine","Tryptophan","Xanthine","PE(18:0/18:3)","Deoxyguanosine","D-Glucosamine","Quinic acid","Choline","S-D-Lactoylglutathione","Asparagine","N-Acetyl-L-alanine","methylglyoxal-hydroimidazolone","LPI(18:3)","2-Ketohexanoic acid","PG(16:0/18:1)","TG58:8-FA22:5","Thymidine","Diphenylamine","D-Fructose 6-phosphate","L-Dihydroorotic acid","4-Hydroxyphenyllactate","TG58:8-FA22:6","Chenodeoxyglycocholic acid","Nicotinamide N-oxide","LPE(20:2)","BMP(16:0/16:0)","UDP","SM 32:1;4","LPC(20:1)","Isobutyrylglycine","Inositol","LPI(18:2)","FA(20:4)","Hexose Monophosphate Pool","Indole-3-acetaldehyde","Indoxyl sulfate","Phosphorylcholine","N1-Methyl-2-pyridone-5-carboxamide","PI(20:0/18:2)","Glycyl-L-leucine","Cyanocobalamin","S-Adenosylhomocysteine","Glucosepane","Gamma-glutamyl-Isoleucine","Isocitrate","DG(18:1/22:6)","Oxypurinol","L-Homocysteine","5'-Deoxyadenosine","LPE(20:3)","Tetrahydroxy-5beta-cholanoic acid","Isovalerylglycine","FA(22:1)","2-Methylcitrate","Allantoic acid","Epinephrine (E)","PC(18:2/22:5)","Leucine","2,3-Diphospho-D-glycerate","Citramalic acid","p-Cresol","Azelaic acid","Dihydrothymine","Carnitine-C5:1","Ribose","L-Carnosine","Hydroxybenzoic acid","p-Aminobenzoic acid","N-Acetyl-L-leucine","L-2-Aminoadipic acid","Isopentenyladenosine","Salicyluric acid","gamma-L-Glutamyl-L-phenylalanine","FA(22:0)","PG(16:0/18:2)","GALA","2,3-Dihydroxybenzoic acid","Deoxycholic acid","Threonate","Carbamoyl phosphate","14,15-Epoxy-5,8,11-eicosatrienoic acid","Glycodeoxycholic acid","5-Hydroxy-L-tryptophan","15-Hydroxyeicosatetraenoic acid","DG(16:1/18:3)","Biopterin","LPE(20:1)"],"additional_accession":[]},"is_claimable":false,"name":"targeted metabolomics of rat's kidney","description":"Podophyllotoxin (PPT) exhibits limited clinical utility due to its nephrotoxicity, and its underlying mechanisms remain poorly understood. This study employs the toxicological evidence chain (TEC) framework and integrated multi-omics analyses to investigate the potential involvement of the microbiota-gut-kidney (MGK) axis in PPT- induced nephrotoxicity in SD rats. Toxicity was systematically evaluated through longitudinal monitoring of body weight, general behavior, biochemical markers, intestinal barrier function, and histopathological alterations. In parallel, multi-omics analyses, encompassing microbiome, metabolomics, and transcriptomics, were conducted to delineate the mechanistic underpinnings. The results showed that PPT exposure induced pronounced renal and intestinal damage, manifesting as significant weight loss, diarrhea, elevated renal injury biomarkers, increased lipopolysaccharide (LPS) levels, and diamine oxidase (DAO), along with histopathological lesions and enhanced apoptosis in renal and colonic tissues. PPT exposure perturbed gut microbiota homeostasis, characterized by depletion of beneficial taxa (e.g., Lactobacillus) and enrichment of potentially pathogenic genera (e.g., Bacteroides and Aggregatibacter), concomitant with diminished short-chain fatty acid (SCFA) production and altered metabolite profiles in fecal, serum, and renal samples. Integrated multi- omics analysis further revealed activation of the JAK1/2-STAT3 signaling pathway, upregulation of pro-inflammatory mediators (TNF-α, IL-6, IL-1β, LPS, and TMAO), and suppression of anti-inflammatory cytokines (IL-10 and IL-4). These in vivo molecular and inflammatory patterns were partially reproduced in HK-2 cells co-cultured with fecal microbiota supernatant from PPT-treated rats. In addition, the JAK1/2 inhibitor ruxolitinib attenuated PPT-induced JAK1/2-STAT3 phosphorylation and inflammatory cytokine secretion in HK-2 cells. Correlation network analysis further identified associations between gut dysbiosis, systemic inflammation, and metabolic perturbations. Collectively, these findings support a mechanistic hypothesis that MGK- axis disruption and JAK1/2-STAT3 signaling may contribute to PPT-associated nephrotoxicity. However, in vivo interventional studies are required to establish definitive causality.","dates":{"publication":"2026-06-28","submission":"2026-06-28"},"accession":"MTBLS14869","cross_references":{}}