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1.
J Funct Biomater ; 14(7)2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37504843

ABSTRACT

Platinum nanoparticles (nPts) have neuroprotective/antioxidant properties, but the mechanisms of their action in cerebrovascular disease remain unclear. We investigated the brain bioavailability of nPts and their effects on brain damage, cerebral blood flow (CBF), and development of brain and systemic oxidative stress (OS) in a model of cerebral ischemia (hemorrhage + temporary bilateral common carotid artery occlusion, tBCAO) in rats. The nPts (0.04 g/L, 3 ± 1 nm diameter) were administered to rats (N = 19) intraperitoneally at the start of blood reperfusion. Measurement of CBF via laser Doppler flowmetry revealed that the nPts caused a rapid attenuation of postischemic hypoperfusion. The nPts attenuated the apoptosis of hippocampal neurons, the decrease in reduced aminothiols level in plasma, and the glutathione redox status in the brain, which were induced by tBCAO. The content of Pt in the brain was extremely low (≤1 ng/g). Thus, nPts, despite the extremely low brain bioavailability, can attenuate the development of brain OS, CBF dysregulation, and neuronal apoptosis. This may indicate that the neuroprotective effects of nPts are due to indirect mechanisms rather than direct activity in the brain tissue. Research on such mechanisms may offer a promising trend in the treatment of acute disorders of CBF.

2.
Lab Med ; 52(1): 47-56, 2021 Jan 04.
Article in English | MEDLINE | ID: mdl-32702115

ABSTRACT

OBJECTIVE: To determine whether urine S-adenosylmethionine (SAM) might be an indicator of chronic kidney disease (CKD). METHODS: We investigated urine levels of SAM and related metabolites (S-adenosylhomocysteine and homocysteine cysteine) in 62 patients (average age, 65.9 years) with CKD (stages II-V). RESULTS: Patients with stages III-V CKD stages have significantly decreased urine levels and SAM/S-adenosylhomocysteine ratio and also cysteine/homocysteine ratio in blood plasma (P <.05), compared with patients with stage II CKD. Urine SAM levels allowed us to distinguish patients with mildly decreased kidney function from those with moderate to severe renal impairment (AUC, 0.791; sensitivity, 85%; specificity, 78.6%). CONCLUSIONS: Our study results demonstrate that urine SAM is a potent biomarker for monitoring renal function decline at early CKD stages. Urine SAM testing confers an additional advantage to healthcare professionals in that it is noninvasive.


Subject(s)
Homocysteine/blood , Renal Insufficiency, Chronic/urine , S-Adenosylhomocysteine/urine , S-Adenosylmethionine/urine , Adult , Aged , Aged, 80 and over , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/physiopathology
3.
Lab Med ; 51(1): 80-85, 2020 Jan 02.
Article in English | MEDLINE | ID: mdl-31247080

ABSTRACT

OBJECTIVE: To evaluate the association of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in urine with chronic kidney disease (CKD). METHODS: Case-control study including 50 patients with CKD and 20 healthy volunteers. RESULTS: SAM level and SAM/SAH ratio in urine were significantly lower in patients than in control individuals (P <.001 and P = .01, respectively). The estimated glomerular filtration rate was associated with the SAM level (P = .04) and the SAM/SAH ratio in urine (P = .01). CONCLUSION: CKD is associated not only with the decline in the SAM level but also with the decrease in the SAM/SAH ratio in urine. Thus, use of the urinary SAM/SAH ratio as a noninvasive diagnostic indicator of renal function seems promising.


Subject(s)
Renal Insufficiency, Chronic/urine , S-Adenosylhomocysteine/urine , S-Adenosylmethionine/urine , Adult , Aged , Aged, 80 and over , Biomarkers/urine , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/diagnosis
4.
Electrophoresis ; 41(3-4): 209-214, 2020 02.
Article in English | MEDLINE | ID: mdl-31779046

ABSTRACT

A new approach for direct determination of S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and methylthioadenosine (MTA) in urine was developed based on MEKC by using SDS modified with isobutanol in the presence of PEG-300. Analytes were first extracted with grafted phenylborononic acid. Using a 50 µm internal diameter silica capillary of 32 cm total length filled with 0.05 M SDS, 0.05 M H3 PO4 , 5% (v/v) isobutanol, and 10% (v/v) PEG-300, LOQ of 0.15 µM for SAM and SAH, and 0.2 µM for MTA was reached. Accuracy was 92% for MTA, 109% for SAH, and 105% for SAM, intra- and interday imprecision were <2.5 and ≤3%, respectively. The total time of analysis for one sample was 10 min. Analysis of 30 urine samples from healthy volunteers showed that the median SAM and SAH levels were 12.1 and 0.73 µM, respectively. MTA levels, which were determined in urine for the first time (according to our data), were 0.43 µM, and these values correlated well with the SAM level (r = 0.748, p < 0.01).


Subject(s)
Adenosine/analogs & derivatives , Chromatography, Micellar Electrokinetic Capillary/methods , S-Adenosylhomocysteine/urine , S-Adenosylmethionine/urine , Thionucleosides/urine , Adenosine/urine , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Limit of Detection , Linear Models , Male , Middle Aged , Reproducibility of Results , Young Adult
5.
Article in English | MEDLINE | ID: mdl-31295723

ABSTRACT

A validated approach to determine various methionine cycle metabolites (S-adenosylmethionine, S-adenosylhomocysteine, and methylthioadenosine) in human blood plasma is offered. The approach is based on solid-phase extraction (with grafted phenylboronic acid) and derivatization with chloroacetaldehyde followed by ultra-performance liquid chromatography with fluorescence detection. We used a 100 × 2.1 mm × 1.8 µm C18 column for the selective separation of analytes. Chromatographic separation was achieved with gradient elution of acetonitrile (flow rate 0.2 mL/min) from 2 to 20%. The eluent was initially composed of 10 mM KH2PO4 with 10 mM acetic acid and 25 µM heptafluorobutyric acid. The total analysis time was 11 min. Validation of the method included detection of the limit of detection (2 nM), limit of quantification (5 nM), accuracy (97.2-101%), and intra- and interday precision (2.2-9.0%). Analysis of plasma samples from healthy volunteers revealed that the average levels of S-adenosylmethionine, S-adenosylhomocysteine, and methylthioadenosine were 93.6, 20.9 and 14.8 nM, respectively.


Subject(s)
Chromatography, High Pressure Liquid/methods , S-Adenosylhomocysteine/blood , S-Adenosylmethionine/blood , Chromatography, High Pressure Liquid/instrumentation , Fluorescence , Humans , Plasma/chemistry , S-Adenosylhomocysteine/isolation & purification , S-Adenosylmethionine/isolation & purification , Solid Phase Extraction
6.
Clin Neurol Neurosurg ; 183: 105393, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31255893

ABSTRACT

OBJECTIVES: To determine the disruption of low-molecular-weight aminothiols (LMWTs: cysteine, cysteinylglycine, homocysteine, and glutathione) homeostasis in blood plasma during the acute and early subacute stages after ischemic stroke. PATIENTS AND METHODS: We admitted 41 patients with primary large-artery atherosclerosis and cardioembolic stroke in the carotid arteries within the first 6-24 h from the moment of neurologic symptoms development. We included 31 patients with chronic cerebral ischemia in the control group. Total LMWT levels and their reduced forms were measured in blood plasma on the 1st, 3rd, 7th, and 15th days after stroke. RESULTS: Our study demonstrated a decrease of cysteine and cysteinylglycine reduced forms and an increase of total glutathione and cysteine levels. There were no differences in LMWT levels among stroke subtypes (large-artery atherosclerosis and cardioembolic stroke). The decrease (or increase) in GSH and Hcy redox status on the 3rd day after stroke was associated with severe neurological deficit. Total Hcy (1st day), Cys (3rd day) and CG(7th day) levels were associated with the size of cerebral infarction area. Logistic regression analysis indicated that reduced homocysteine, total cysteinylglycine levels, and cysteine redox status at admission were predictive factors for ischemic stroke occurrence with a probability of 86.2% (p < 0.001). CONCLUSIONS: LMWTs may indicate the severity of neurological deficit and the size of the cerebral infarct, and their complex determination can be of diagnostic importance both at an early stage of ischemic stroke development and during its monitoring.


Subject(s)
Brain Ischemia/blood , Disulfides/blood , Homeostasis/physiology , Stroke/blood , Sulfhydryl Compounds/blood , Female , Glutathione/blood , Humans , Male , Middle Aged , Oxidative Stress/physiology , Risk Factors
7.
J Cardiovasc Pharmacol ; 72(4): 195-203, 2018 10.
Article in English | MEDLINE | ID: mdl-30188870

ABSTRACT

Cerebral ischemia has previously been shown to cause a systemic decrease in levels of the reduced forms of low-molecular-weight aminothiols [cysteine (Cys), homocysteine (Hcy), and glutathione (GSH)] in blood plasma. In this study, we examined the effect of beta-adrenergic receptor (ß-AR) antagonists metoprolol (Met) and nebivolol (Neb) on the redox status of these aminothiols during acute cerebral ischemia in rats. We used a model of global cerebral ischemia (bilateral occlusion of common carotid arteries with hypotension lasting for 10 minutes). The antagonists were injected 1 hour before surgery. Total and reduced Cys, Hcy, and GSH levels were measured 40 minutes after the start of reperfusion. Neb (0.4 and 4 mg/kg) and Met (8 and 40 mg/kg) treatment increased the levels of reduced aminothiols and the global methylation index in the hippocampus. The treatments also prevented any decrease in reduced aminothiol levels in blood plasma during ischemia. Although both of these drugs eliminated delayed postischemic hypoperfusion, only Neb reduced neuronal damage in the hippocampus. The results indicate an essential role of ß1-AR blockage in the maintenance of redox homeostasis of aminothiols in the plasma and brain during acute cerebral ischemia.


Subject(s)
Adrenergic beta-1 Receptor Antagonists/pharmacology , Brain Ischemia/drug therapy , Cysteine/blood , Glutathione/blood , Hippocampus/drug effects , Homocysteine/blood , Metoprolol/pharmacology , Nebivolol/pharmacology , Neuroprotective Agents/pharmacology , Acute Disease , Animals , Brain Ischemia/blood , Brain Ischemia/pathology , Brain Ischemia/physiopathology , Cerebrovascular Circulation/drug effects , Disease Models, Animal , Hippocampus/metabolism , Hippocampus/pathology , Male , Molecular Weight , Oxidation-Reduction , Rats
8.
Electrophoresis ; 38(20): 2646-2653, 2017 10.
Article in English | MEDLINE | ID: mdl-28681932

ABSTRACT

A rapid and selective method has been developed for highly sensitive determination of total cysteine and homocysteine levels in human blood plasma and urine by capillary electrophoresis (CE) coupled with liquid-liquid extraction. Analytes were first derivatized with 1,1'-thiocarbonyldiimidazole and then samples were purified by chloroform-ACN extraction. Electrophoretic separation was performed using 0.1 M phosphate with 30 mM triethanolamine, pH 2, containing 25 µM CTAB, 2.5 µM SDS, and 2.5% polyethylene glycol 600. Samples were injected into the capillary (with total length 32 cm and 50 µm id) at 2250 mbar*s and subsequent injection was performed for 30 s with 0.5 M KОН. The total analysis time was less than 9 min, accuracy was 98%, and precision was <2.6%. The LOD was 0.2 µM for homocysteine and 0.5 µM for cysteine. The use of liquid-liquid extraction allowed the precision and sensitivity of the CE method to be significantly increased. The validated method was applied to determine total cysteine and homocysteine content in human blood plasma and urine samples obtained from healthy volunteers and patients with kidney disorders.


Subject(s)
Cysteine/blood , Cysteine/urine , Electrophoresis, Capillary/methods , Homocysteine/blood , Homocysteine/urine , Liquid-Liquid Extraction/methods , Acetonitriles/chemistry , Adolescent , Adult , Aged , Aged, 80 and over , Chloroform/chemistry , Female , Humans , Limit of Detection , Middle Aged , Sensitivity and Specificity , Young Adult
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