Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock

Gamarra, Yenifer; Santiago, F.; Molina-López, Jorge; Castaño, José; Herrera-Quintana, Lourdes; Domínguez, Álvaro; Planells, Elena

doi:10.1186/s13054-019-2450-5

Cited by 39 publications

(23 citation statements)

References 47 publications

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“…Glutathione is decomposed into L-gammaglutamyl amino acid, and L-gamma-glutamyl amino acid is further converted to pyroglutamic acid. A high level of pyroglutamic acid also contributes to glutathione de ciency and could be an indicator of the oxidative state [61]. Similarly, in our study, the concentration of pyroglutamic acid was signi cantly downregulated.…”

Section: The Altered Pathways Of Amino Acid Metabolism and Lipid Metasupporting

confidence: 78%

Antioxidant Potential of Pediococcus Pentosaceus Strains From the Sow Milk Bacterial Collection in Weaned Piglets

Wang

Liu

Zhou

et al. 2020

Preprint

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Background: In modern animal husbandry, the relationship between sow and piglets is closely linked as breeders pay more attention to improving sow nutrition during pregnancy and lactation to favor the growing of neonates. Sow milk is the main food for piglets during their first three weeks of life, which is not only a rich repository of essential nutrients and a broad range of bioactive compounds, but also an indispensable source of commensal bacteria. Maternal milk microorganisms are important sources of commensal bacteria for neonatal gut. Bacteria from hosts’ maternal milk may serve as an additive to confer a health benefit on the composition of the indigenous microbiota of piglets.Methods: We first obtained isolates from the sow milk microbiota by the culturomics methods of continuous culture and interval sampling. Then, identified and grouped them based on a nonredundant set of 16S rDNA gene sequences. After assessing their antimicrobial activity against enteropathogens in vitro, we selected several strains to further conduct assay in Drosophila to evaluate their resistance against oxidative injury. We finally screened out Pediococcus pentosaceus (P. pentosaceus) SMM914 as candidate strain to verify its antioxidant effect in weaned piglets and study its probiotic function by 16S rDNA sequencing, metabolomics, western blotting and enzyme activity analysis.Results: The 1240 isolates were screened out from the sow milk microbiota and grouped into 271 bacterial taxa. We evaluated 80 Pediococcus isolates about their inhibition ability against enteropathogens in vitro and then chose top 10 isolates to further test them in Drosophila. In 80 Pediococcus isolates, P. pentosaceus SMM914 showed best performance by inhibition ability against enteropathogens in vitro andparaquat challenge in Drosophila model. Pretreatment of piglets with SMM914 induces the Nrf2/Keap1 antioxidant signaling pathway and altered the pathways of amino acid metabolism and lipid metabolism in plasma. In colon, Lactobacillus was significantly increased in the high dose of SMM914 group compared with the control group.Conclusion: Our study provided useful resources for deeply understanding the relationships between the maternal microbiota and the offspring and supported the theory of Sow and Piglet Integration.

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Section: The Altered Pathways Of Amino Acid Metabolism and Lipid Metasupporting

confidence: 78%

Antioxidant Potential of Pediococcus Pentosaceus Strains From the Sow Milk Bacterial Collection in Weaned Piglets

Wang

Liu

Zhou

et al. 2020

Preprint

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“…Serum 5-oxo-proline as measured by MSI-CE-MS was found to be elevated in both early and late-stage fibrosis HCV patients as compared to non-HCV controls ( Figure 5C ). Oxo-proline (or pyroglutamic acid) is an important yet infrequently measured amino acid intermediate within the glutathione cycle ( Bachhawat and Yadav, 2018 ), which accumulates in circulation due to acquired 5-oxoprolinemia from hepatic oxidative insult and glutathione depletion ( Gamarra et al, 2019 ). However, most studies to date have focused on a high anion gap metabolic acidosis from 5-oxoprolinemia following sepsis or acetaminophen toxicity ( Liss et al, 2013 ) rather than liver fibrosis/inflammation from chronic HCV infection or non-alcoholic steatohepatitis ( Saoi et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

A Cross-Platform Metabolomics Comparison Identifies Serum Metabolite Signatures of Liver Fibrosis Progression in Chronic Hepatitis C Patients

Shanmuganathan

Sarfaraz

Kroezen

et al. 2021

Front. Mol. Biosci.

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Metabolomics offers new insights into disease mechanisms that is enhanced when adopting orthogonal instrumental platforms to expand metabolome coverage, while also reducing false discoveries by independent replication. Herein, we report the first inter-method comparison when using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) and nuclear magnetic resonance (NMR) spectroscopy for characterizing the serum metabolome of patients with liver fibrosis in chronic hepatitis C virus (HCV) infection (n = 20) and non-HCV controls (n = 14). In this study, 60 and 30 serum metabolites were detected frequently (>75%) with good technical precision (median CV < 10%) from serum filtrate samples (n = 34) when using standardized protocols for MSI-CE-MS and NMR, respectively. Also, 20 serum metabolite concentrations were consistently measured by both methods over a 500-fold concentration range with an overall mean bias of 9.5% (n = 660). Multivariate and univariate statistical analyses independently confirmed that serum choline and histidine were consistently elevated (p < 0.05) in HCV patients with late-stage (F2-F4) as compared to early-stage (F0-F1) liver fibrosis. Overall, the ratio of serum choline to uric acid provided optimal differentiation of liver disease severity (AUC = 0.848, p = 0.00766) using a receiver operating characteristic curve, which was positively correlated with liver stiffness measurements by ultrasound imaging (r = 0.606, p = 0.0047). Moreover, serum 5-oxo-proline concentrations were higher in HCV patients as compared to non-HCV controls (F = 4.29, p = 0.0240) after adjustment for covariates (age, sex, BMI), indicative of elevated oxidative stress from glutathione depletion with the onset and progression of liver fibrosis. Both instrumental techniques enable rapid yet reliable quantification of serum metabolites in large-scale metabolomic studies with good overlap for biomarker replication. Advantages of MSI-CE-MS include greater metabolome coverage, lower operating costs, and smaller sample volume requirements, whereas NMR offers a robust platform supported by automated spectral and data processing software.

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“…When there is abundant GSH, it suppresses its own production by blocking γ-glutamyl cysteine synthase (γ-Gcs). Otherwise, GSH depletion results in increased γ-Gcs, leading to accumulation of pyroglutamic acid (76).…”

Section: The Role Of Gsh Systemmentioning

confidence: 99%

Centrality of G6PD in COVID-19: The Biochemical Rationale and Clinical Implications

Buinitskaya¹,

Gurinovich²,

Wlodaver

et al. 2020

Front. Med.

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Introduction: COVID-19 is a novel and devastating disease. Its manifestations vary from asymptomatic to lethal. Moreover, mortality rates differ based on underlying health conditions and ethnicity. We investigated the biochemical rationale behind these observations using machine reasoning by the sci.AI system (https://sci.ai/). Facts were extracted and linked from publications available in nlm.nih.gov and Europe PMC to form the dataset which was validated by medical experts. Results: Based on the analysis of experimental and clinical data, we synthesized detailed biochemical pathways of COVID-19 pathogenesis which were used to explain epidemiological and clinical observations. Clinical manifestations and biomarkers are highlighted to monitor the course of COVID-19 and navigate treatment. As depicted in the Graphical Abstract, SARS-CoV-2 triggers a pro-oxidant (PO) response leading to the production of reactive oxygen species (ROS) as a normal innate defense. However, SARS-CoV-2's unique interference with the antioxidant (AO) system, through suppression of nitric oxide (NO) production in the renin-angiotensin-aldosterone system (RAAS), leads to an excessive inflammatory PO response. The excessive PO response becomes critical in cohorts with a compromised AO system such as patients with glucose-6-phosphate dehydrogenase deficiency (G6PDd) where NO and glutathione (GSH) mechanisms are impaired. G6PDd develops in patients with metabolic syndrome. It is mediated by aldosterone (Ald) which also increases specifically in COVID-19. Conclusion: G6PD is essential for an adequate immune response. Both G6PDd and SARS-CoV-2 compromise the AO system through the same pathways rendering G6PDd the Achilles' heel for COVID-19. Thus, the evolutionary antimalarial advantage of the G6PDd cohort can be a disadvantage against SARS-CoV-2.

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Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock

Cited by 39 publications

References 47 publications

Antioxidant Potential of Pediococcus Pentosaceus Strains From the Sow Milk Bacterial Collection in Weaned Piglets

Antioxidant Potential of Pediococcus Pentosaceus Strains From the Sow Milk Bacterial Collection in Weaned Piglets

A Cross-Platform Metabolomics Comparison Identifies Serum Metabolite Signatures of Liver Fibrosis Progression in Chronic Hepatitis C Patients

Centrality of G6PD in COVID-19: The Biochemical Rationale and Clinical Implications

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