GNPS - Carnitine Blood Plasma Samples- Acute and Chronic Stage - Positive Mode
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Trypanosoma Cruzi (ncbitaxon:5693) Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Laura-Isobel McCall
PROVIDER: MSV000084016 | GNPS | Thu Jun 27 13:16:00 BST 2019
REPOSITORIES: GNPS
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Project description:Samples from mice infected and then treated with vehicle, carnitine or benznidazole in the chronic stage of infection. Tissue samples extracted with 50% methanol followed by 3:1 dichloromethane:methanol. C8 chromatography with negative mode data acquisition
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Project description:Large intestine samples from mice infected with 50,000 Trypanosoma cruzi parasites or left uninfected. One week post-infection, mice were treated with carnitine, benznidazole or vehicle. Animals were euthanized after 10 days of treatment and organs collected. Metabolites were extracted with 50% methanol followed by 3:1 dichloromethane-methanol and analyzed by C8 chromatography, with positive mode ddMS2 data collection (data-dependent).
2020-03-24 | MSV000085142 | GNPS
Project description:Male C3H/HeJ mice were infected with 50,000 luciferase-expressing strain CL Brener trypanosoma cruzi parasites. Beginning 7 days post-infection, mice were treated with carnitine in drinking water (100 mg/kg/day dosing equivalent), benznidazole (100 mg/kg/day by intraperitoneal injection), or left untreated (vehicle group). One additional control group was uninfected. Mice were euthanized and liver and oesophagus collected at day 17 post-infection. Tissue was extracted with 50% methanol followed by 3:1 dichloromethane:methanol, and analyzed by C8 chromatography, with detection by MS in positive mode.
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2019-04-05 | MSV000083665 | GNPS
Project description:Large intestine samples from mice infected with 50,000 Trypanosoma cruzi parasites or left uninfected. One week post-infection, mice were treated with carnitine, benznidazole or vehicle. Animals were euthanized after 10 days of treatment and organs collected. Metabolites were extracted with 50% methanol followed by 3:1 dichloromethane-methanol and analyzed by C8 chromatography, with negative mode ddMS2 data collection (data-dependent).
2020-03-24 | MSV000085143 | GNPS
Project description:Samples from mice infected and then treated with vehicle, carnitine or benznidazole in the chronic stage of infection. Tissue samples extracted with 50% methanol followed by 3:1 dichloromethane:methanol. C8 chromatography with negative mode data acquisition
2023-11-13 | MSV000093394 | GNPS
Project description:BACKGROUND:Primary carnitine deficiency (PCD) is a disorder of fatty acid oxidation with a high prevalence in the Faroe Islands. Only patients homozygous for the c.95A>G (p.N32S) mutation have displayed severe symptoms in the Faroese patient cohort. In this study, we investigated carnitine levels in skeletal muscle, plasma, and urine as well as renal elimination kinetics before and after intermission with L-carnitine in patients homozygous for c.95A>G. METHODS:Five male patients homozygous for c.95A>G were included. Regular L-carnitine supplementation was stopped and the patients were observed during five days. Blood and urine were collected throughout the study. Skeletal muscle biopsies were obtained at 0, 48, and 96 h. RESULTS:Mean skeletal muscle free carnitine before discontinuation of L-carnitine was low, 158 nmol/g (SD 47.4) or 5.4% of normal. Mean free carnitine in plasma (fC0) dropped from 38.7 (SD 20.4) to 6.3 (SD 1.7) ?mol/L within 96 h (p?<?0.05). Mean T 1/2 following oral supplementation was approximately 9 h. Renal reabsorption of filtered carnitine following oral supplementation was 23%. The level of mean free carnitine excreted in urine correlated (R (2)?=?0.78, p?<?0.01) with fC0 in plasma. CONCLUSION:Patients homozygous for the c.95A>G mutation demonstrated limited skeletal muscle carnitine stores despite long-term high-dosage L-carnitine supplementation. Exacerbated renal excretion resulted in a short T 1/2 in plasma carnitine following the last oral dose of L-carnitine. Thus a treatment strategy of minimum three daily separate doses of L-carnitine is recommended, while intermission with L-carnitine treatment might prove detrimental.
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Project description:Recent studies have implicated trimethylamine N-oxide (TMAO) in atherosclerosis, raising concern about L-carnitine, a common supplement for patients with inborn errors of metabolism (IEMs) and a TMAO precursor metabolized, in part, by intestinal microbes. Dietary meat restriction attenuates carnitine-to-TMAO conversion, suggesting that TMAO production may not occur in meat-restricted individuals taking supplemental L-carnitine, but this has not been tested. Here, we mine a metabolomic dataset to assess TMAO levels in patients with diverse IEMs, including organic acidemias. These data were correlated with clinical information and confirmed using a quantitative TMAO assay. Marked plasma TMAO elevations were detected in patients treated with supplemental L-carnitine, including those on a meat-free diet. On average, patients with an organic acidemia had ~45-fold elevated [TMAO], as compared to the reference population. This effect was mitigated by metronidazole therapy lasting 7 days each month. Collectively, our data show that TMAO production occurs at high levels in patients with IEMs receiving oral L-carnitine. Further studies are needed to determine the long-term safety and efficacy of chronic oral L-carnitine supplementation and whether suppression or circumvention of intestinal bacteria may improve L-carnitine therapy.
| S-EPMC5110437 | biostudies-literature
Project description:Despite this large body of evidence from clinical studies that an improvement of carnitine status has beneficial effects on metabolic health, serious safety concerns with carnitine supplementation have been raised based on the recent observation that longterm carnitine supplementation (from weaning to 5 mo of age) in a transgenic mouse model of atherosclerosis (Apoe-/- mice) promotes atherosclerosis through gut microbiota-dependent formation of trimethylamine (TMA) and subsequent hepatic conversion into proatherogenic TMA-N-oxide (TMAO) (Koeth et al., 2013). In addition, Lu et al. (2017) found that carnitine supplementation to normal mice for 3 mo induces oxidative stress, liver inflammation, liver lipid accumulation and even liver damage as well as hypercholesterinemia. However, it has to be mentioned that the carnitine dose administered to the mice in the abovementioned studies was extremely high. In order to address whether safety concerns are founded under conditions of longterm supplementation of a carnitine dose used in clinical trials, the present study aimed to investigate the effect of almost lifelong daily administration of a carnitine-supplemented diet (1 g/kg diet) to mice from weaning to 18 mo of age. Considering a body weight of 50 g for an adult mice and a daily feed intake of 5 g, the daily intake of this diet results in a daily carnitine dose of 100 mg/kg body weight which better reflects the dose used in clinical trials. In order to evaluate possible detrimental effects of carnitine supplementation, we investigated parameters of lipid metabolism and stress signaling pathways in the liver and performed a genome-wide transcriptome analysis of skeletal muscle in the mice at advanced age.
2018-09-19 | GSE120120 | GEO
Project description:BackgroundAtherosclerosis is considered the major cause of the dramatic increase in cardiovascular mortality among patients suffering from chronic kidney disease (CKD). Although the close connection between atherosclerosis and kidney dysfunction is undeniable, factors enhancing CKD-mediated plaque formation are still not well recognized.ResultsTo increase our knowledge of this process we carried out a comparative proteomic analysis of blood plasma proteins isolated from 75 patients in various stages of renal dysfunction (CKD group), 25 patients with advanced cardiovascular disease (CVD group) and 25 healthy volunteers (HV group). The collected samples were subjected to 2D electrophoresis. Then, individual proteins were identified by mass spectrometry. The comparative analysis involving CKD and HV groups showed a differential accumulation of ?-1-microglobulin, apolipoprotein A-IV, ?-fibrinogen and haptoglobin in patients with kidney disease. Exactly the same proteins were identified as differentially expressed when proteomes of CVD patients and HV were compared. However, a direct comparison of CKD and CVD groups revealed significant differences in the accumulation of two proteins: ?-1-microglobulin and apolipoprotein A-IV.ConclusionsThe obtained results indicate that at least two processes differentially contribute to the plaque formation in CKD- and CVD-mediated atherosclerosis. It seems that the inflammatory process is more intense in CKD patients. On the other hand, the down- and up-regulation of apolipoprotein A-IV in CVD and CKD groups, respectively, suggests that substantial differences exist in the efficacy of cholesterol transport in both groups of patients.
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