GC-MS validation and analysis of targeted plasma metabolites related to carbonyl stress in type 2 diabetes mellitus patients with and without acute coronary syndrome.

Methylglyoxal (MG) is responsible for advanced glycation end-product formation, the mechanisms leading to diabetes pathogenesis and complications like acute coronary syndrome (ACS). Sugar metabolites, amino acids and fatty acids are possible substrates for MG. The study aimed to measure plasma MG substrate levels using a validated gas chromatography-mass spectrometry (GC-MS) method and explore their association with ACS risk in type 2 diabetes mellitus (T2DM). The study included 150 T2DM patients with ACS as cases and 150 T2DM without ACS as controls for the analysis of glucose, fructose, ribulose, sorbitol, glycerol, pyruvate, lactate, glycine, serine, threonine, C16:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:0 and C22:6 by GC-MS. Validated GC-MS methods were accurate, precise and sensitive. Cases significantly differed in plasma MG and metabolite levels except for lactate, C16:0, C18:0, C18:2, and C18:3 levels compared with controls. On multivariable logistic regression, plasma C20:0, C18:1, glycine and glycerol levels had increased odds of ACS risk. On multivariate receiver operating characteristic analysis, a model containing plasma C20:0, C16:1, C18:1, C18:2, serine, glycerol, lactate and threonine levels had the highest area under the curve value (0.932) for ACS diagnosis. In conclusion, plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol levels were associated with ACS risk in T2DM.

Evaluation of changes in carbonyl stress markers with treatment in male patients with bipolar disorder manic episode: A controlled study.

BACKGROUND: Carbonyl stress, a metabolic state characterized by elevated production of reactive carbonyl compounds (RCCs), is closely related to oxidative stress and has been implicated in various diseases. This study aims to investigate carbonyl stress parameters in drug-free bipolar disorder (BD) patients compared to healthy controls, explore their relationship with clinical features, and assess the effect of treatment on these parameters. METHODS: Patients with a primary diagnosis of a manic episode of BD and healthy controls were recruited. Exclusion criteria included intellectual disability, presence of neurological diseases, chronic medical conditions such as diabetes mellitus and metabolic syndrome, and clinical signs of inflammation. Levels of serum carbonyl stress parameters were determined using high-performance liquid chromatography. RESULTS: Levels of glyoxal (GO) and methylglyoxal (MGO) did not differ between pre- and post-treatment patients, but malondialdehyde (MDA) levels decreased significantly post-treatment. Pre-treatment MGO and MDA levels were higher in patients compared to controls, and these differences persisted post-treatment. After adjusting for BMI and waist circumference, only MDA levels remained significantly higher in patients compared to controls. LIMITATIONS: The study's limitations include the exclusion of female patients, which precluded any assessment of potential gender differences, and the lack of analysis of the effect of specific mood stabilizers or antipsychotic drugs. CONCLUSIONS: This study is the first to focus on carbonyl stress markers in BD, specifically GO, MGO, and MDA. MDA levels remained significantly higher in patients, suggesting a potential role in BD pathophysiology. MGO levels were influenced by metabolic parameters, indicating a potential link to neurotoxicity in BD. Further research with larger cohorts is needed to better understand the role of RCCs in BD and their potential as therapeutic targets.

Placental Methylglyoxal in Preeclampsia: Vascular and Biomarker Implications.

BACKGROUND: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction. METHODS: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies. Uncomplicated placentas and trophoblast cells (BeWo) were exposed to hypoxia. The reactive dicarbonyl MGO and advanced glycation end products (Nε-(carboxymethyl)lysine [CML], Nε-(carboxyethyl)lysine [CEL], and MGO-derived hydroimidazolone [MG-H]) were quantified using liquid chromatography-tandem mass spectrometry. The activity of GLO1 (glyoxalase-1), that is, the enzyme detoxifying MGO, was measured. The impact of MGO on vascular function was evaluated using wire/pressure myography. The therapeutic potential of the MGO-quencher quercetin and mitochondrial-specific antioxidant mitoquinone mesylate (MitoQ) was explored. RESULTS: MGO, CML, CEL, and MG-H2 levels were elevated in preeclampsia-placentas (+36%, +36%, +25%, and +22%, respectively). Reduced GLO1 activity was observed in preeclampsia-placentas (-12%) and hypoxia-exposed placentas (-16%). Hypoxia-induced MGO accumulation in placentas was mitigated by the MGO-quencher quercetin. Trophoblast cells were identified as the primary source of MGO. Reduced GLO1 activity was also observed in hypoxia-exposed BeWo cells (-26%). Maternal plasma concentrations of CML and the MGO-derived MG-H1 increased as early as 12 weeks of gestation (+16% and +17%, respectively). MGO impaired endothelial barrier function, an effect mitigated by MitoQ, and heightened vascular responsiveness to thromboxane A2. CONCLUSIONS: This study reveals the accumulation of placental MGO in preeclampsia and upon exposure to hypoxia, demonstrates how MGO can contribute to vascular impairment, and highlights plasma CML and MG-H1 levels as promising early biomarkers for preeclampsia.