Metabolomic Alteration in the Plasma of Wild Rodents Environmentally Exposed to Lead: A Preliminary Study

Lead poisoning is often considered a traditional disease; however, the specific mechanism of toxicity remains unclear. The study of Pb-induced alterations in cellular metabolic pathways is important to understand the biological response and disorders associated with environmental exposure to lead. Metabolomics studies have recently been paid considerable attention to understand in detail the biological response to lead exposure and the associated toxicity mechanisms. In the present study, wild rodents collected from an area contaminated with lead (N = 18) and a control area (N = 10) were investigated. This was the first ever experimental metabolomic study of wildlife exposed to lead in the field. While the levels of plasma phenylalanine and isoleucine were significantly higher in a lead-contaminated area versus the control area, hydroxybutyric acid was marginally significantly higher in the contaminated area, suggesting the possibility of enhancement of lipid metabolism. In the interregional least-absolute shrinkage and selection operator (lasso) regression model analysis, phenylalanine and isoleucine were identified as possible biomarkers, which is in agreement with the random forest model. In addition, in the random forest model, glutaric acid, glutamine, and hydroxybutyric acid were selected. In agreement with previous studies, enrichment analysis showed alterations in the urea cycle and ATP-binding cassette transporter pathways. Although regional rodent species bias was observed in this study, and the relatively small sample size should be taken into account, the present results are to some extent consistent with those of previous studies on humans and laboratory animals.

Which Role Plays 2-Hydroxybutyric Acid on Insulin Resistance?

Type 2 Diabetes Mellitus (T2D) is defined as a chronic condition caused by beta cell loss and/or dysfunction and insulin resistance (IR). (1) Background: The discovering of novel biomarkers capable of identifying T2D and other metabolic disorders associated with IR in a timely and accurate way is critical. In this review, 2-hydroxybutyric acid (2HB) is presented as that upheaval biomarker with an unexplored potential ahead. Due to the activation of other metabolic pathways during IR, 2HB is synthesized as a coproduct of protein metabolism, being the progression of IR intrinsically related to the increasing of 2HB levels. Hence, the focus of this review will be on the 2HB metabolite and its involvement in glucose homeostasis. (2) Methods: A literature review was conducted, which comprised an examination of publications from different databases that had been published over the previous ten years. (3) Results: A total of 19 articles fulfilled the intended set of criteria. The use of 2HB as an early indicator of IR was separated into subjects based on the number of analytes examined simultaneously. In terms of the association between 2HB and IR, it has been established that increasing 2HB levels can predict the development of IR. (4) Conclusions: Thus, 2HB has demonstrated considerable promise as a clinical monitoring molecule, not only as an IR biomarker, but also for disease follow-up throughout IR treatment.

Gamma-hydroxybutyric acid-induced organic delirium complicated by polydrug use successfully treated with electroconvulsive therapy: a case report

Background Patients with gamma-hydroxybutyric acid withdrawal symptoms are at high risk of developing organic delirium, which can be fatal. The recommended first-line treatment is benzodiazepines, but treatment-resistant cases are frequent. Here we describe a case of successful bilateral electroconvulsive therapy in a patient with severe and highly agitated acute organic delirium induced by gamma-hydroxybutyric acid withdrawal and complicated by polydrug use resistant to first-line treatment. To our knowledge, this is the first report on the effect of electroconvulsive therapy on treatment-resistant delirium caused by gamma-hydroxybutyric acid withdrawal. Case presentation A 21-year-old Danish man diagnosed with untreated attention deficit hyperactivity disorder developed severely agitated acute organic delirium caused by gamma-hydroxybutyric acid withdrawal in a Danish psychiatric ward. The patient was subjected to physical restraints and transferred to the intensive care unit for treatment. During the next 10 days, the patient showed no clinical improvement despite first-line, high-dose benzodiazepines along with intense supportive treatment with propofol, phenobarbital, and antipsychotics. On day 11, bilateral frontotemporal electroconvulsive therapy treatment was initiated and full clinical recovery was obtained after four sessions. Discussion The full clinical remission after four electroconvulsive therapy sessions, strongly supports that electroconvulsive therapy may be an effective treatment when severe delirium induced by gamma-hydroxybutyric acid withdrawal is resistant to conventional first-line treatment with benzodiazepines. Moreover, this case illustrates that clinically effective seizures were achieved despite intensive concurrent exposure to anticonvulsive drugs. Therefore, this case report encourages consideration of electroconvulsive therapy in patients with gamma-hydroxybutyric acid delirium who are resistant to psychopharmacological treatment.

Gas Chromatography–Mass Spectroscopy-Based Metabolomics Analysis Reveals Potential Biochemical Markers for Diagnosis of Gestational Diabetes Mellitus

Due to many adverse effects of gestational diabetes mellitus (GDM) on the mother and fetus, its diagnosis is crucial. The presence of GDM can be confirmed by an abnormal fasting plasma glucose level (aFPG) and/or oral glucose tolerance test (OGTT) performed mostly between 24 and 28 gestational week. Both aFPG and abnormal glucose tolerance (aGT) are used to diagnose GDM. In comparison to measurement of FPG, OGTT is time-consuming, usually inconvenient for the patient, and very often needs to be repeated. Therefore, it is necessary to seek tests that will be helpful and convenient to diagnose GDM. For this reason, we investigated the differences in fasting serum metabolites between GDM women with abnGM and normal FPG (aGT-GDM group), with aFPG and normal glucose metabolism (aFPG-GDM group) as well as pregnant women with normal glucose tolerance (NGT) being a control group. Serum metabolites were measured by an untargeted approach using gas chromatography–mass spectrometry (GC–MS). In the discovery phase, fasting serum samples collected from 79 pregnant women (aFPG-GDM, n = 24; aGT-GDM, n = 26; NGT, n = 29) between 24 and 28 weeks of gestation (gwk) were fingerprinted. A set of metabolites (α–hydroxybutyric acid (α–HB), β–hydroxybutyric acid (β–HB), and several fatty acids) significant in aGT-GDM vs NGT but not significant in aFPG-GDM vs NGT comparison in the discovery phase was selected for validation. These metabolites were quantified by a targeted GC–MS method in a validation cohort consisted of 163 pregnant women (aFPG-GDM, n = 51; aGT-GDM, n = 44; and NGT, n = 68). Targeted analyses were also performed on the serum collected from 92 healthy women in the first trimester (8–14 gwk) who were NGT at this time, but in the second trimester (24–28 gwk) they were diagnosed with GDM. It was found that α–HB, β–HB, and several fatty acids were associated with aGT-GDM. A combination of α–HB, β–HB, and myristic acid was found highly specific and sensitive for the diagnosis of GDM manifested by aGT-GDM (AUC = 0.828) or to select women at a risk of aGT-GDM in the first trimester (AUC = 0.791). Our findings provide new potential markers of GDM and may have implications for its early diagnosis.