Search Results (26)

This report presents the first method for simultaneous determination of the 2-S-lepidinium derivatives of total α-lipoic acid (LA), homocysteine (Hcy), cysteinylglycine (CysGly), and cysteine (Cys) in human saliva, using capillary electrophoresis with pH-mediated sample stacking and ultraviolet detection (CE-UV) at 355 nm. Electrophoretic separation is carried out at 20 kV and 25 °C using a standard fused silica capillary (effective length 91.5 cm, inner diameter 75 µm). The background electrolyte consists of 0.5 mol/L lithium acetate buffer, adjusted to pH 3.5 with 0.5 mol/L acetic acid. The limit of quantification was determined to be 1 µmol/L for LA and 0.17 µmol/L for Hcy, 0.11 µmol/L for CysGly, and 0.10 µmol/L for Cys in saliva samples. Calibration curves demonstrated linearity over the concentration range of 3 to 30 µmol/L for all analytes. Method precision did not exceed 4.7%, and accuracy ranged from 87.9% to 114.0%. The developed method was successfully applied to saliva samples from eleven apparently healthy volunteers to determine the content of LA, Hcy, CysGly, and Cys. The Hcy, CysGly, and Cys concentrations ranged from 0.55 to 13.76 µmol/L, 0.89 to 9.29 µmol/L, and 1.73 to 12.99 µmol/L, respectively. No LA-derived peaks were detected in the native saliva samples. Full article

Background: Data show that due to endothelial damage and thrombogenic effects, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may accelerate the development of atherosclerosis and increase the risk of cardiovascular diseases (CVDs). The impaired metabolism of aminothiols increases oxidative stress, as these molecules are involved in antioxidant defense as well as in thiol redox control. In this study, total levels of selected aminothiols (i.e., cysteine (Cys), homocysteine (HCy), and glutathione) in convalescents after coronavirus disease of 2019 (COVID-19) were evaluated. The analyses were made according to the sex of the patients, time from COVID-19 onset, and COVID-19 severity. Methods: The study group consisted of 212 patients after COVID-19. Levels of total aminothiols were assessed in the blood plasma using high-performance liquid chromatography (HPLC). Results: The mean Cys concentrations were higher in men than in women (229.92 µmol/L ± 51.54 vs. 210.35 µmol/L ± 41.90, respectively; p = 0.003). Differences in Cys levels were also noticed in the total study group between patients distinguished due to time from disease onset (226.82 µmol/L ± 40.57 in <12 weeks, 232.23 µmol/L ± 47.99 in patients 12–24 weeks, and 208.08 µmol/L ± 48.43 in patients >24 weeks; p = 0.005). In addition, over 11% of total patients 12–24 weeks from disease onset had Cys levels above 300 µmol/L compared to almost 4% of patients <12 weeks and 2% of patients >24 weeks (p = 0.046). In sex-adjusted subgroups, significant differences due to time from COVID-19 were found in Cys levels in women (p = 0.004) and in glutathione levels in men (p = 0.024). None of the aminothiol levels differed between the subgroups based on the severity of COVID-19. Conclusions: Men had overall higher Cys levels than women. Cys levels were lower >24 weeks after COVID-19 onset than in the earlier period after disease onset. A partial elevation in Cys levels 12–24 weeks after the disease onset may contribute to the increase in CVD risk in the post-COVID-19 period. Full article

Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine’s inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment. Full article

Cystinosis is a rare lysosomal storage disorder caused by autosomal recessive mutations in the CTNS gene that encodes for the cystine transporter cystinosin, which is expressed on the lysosomal membrane mediating the efflux of cystine. Cysteamine bitartrate is a cystine-depleting aminothiol agent approved for the treatment of cystinosis in children and adults. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the determination of cysteamine levels in plasma samples. This LC-MS/MS method was validated according to the European Medicines Agency (EMA)’s guidelines for bioanalytical method validation. An ultra-performance liquid chromatograph (UPLC) coupled with a 6470 mass spectrometry system was used for cysteamine determination. Our validated method was applied to plasma samples from n = 8 cystinosis patients (median, interquartile range (IQR) = 20.5, 8.5–26.0 years). The samples were collected before cysteamine oral administration (pre-dose) and 1 h after (post-dose). Our bioanalytical method fulfilled the regulatory guidelines for method validation. The cysteamine plasma levels in pre-dose samples were 2.57 and 1.50–3.31 μM (median and IQR, respectively), whereas the post-dose samples reported a cysteamine median concentration of 28.00 μM (IQR: 17.60–36.61). Our method allows the rapid determination of cysteamine plasma levels. This method was successfully used in cystinosis patients and, therefore, could be a useful tool for the evaluation of therapy adherence and for future pharmacokinetic (PK) studies involving a higher number of subjects. Full article

We examined standard clinical and laboratory biochemical parameters, as well as the levels of aminothiols in the blood and urine (homocysteine (Hcy), cysteine (Cys), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH)) via capillary electrophoresis in patients with CKD at stages II–V. Patient outcomes were assessed after five years. To complete forecasting, correlation and ROC analysis were performed. It was found that the levels of Cys and Hcy in blood plasma were earlier markers of CKD starting from stage II, while the levels of SAM and SAM/SAH in urine made it possible to differentiate between CKD at stages II and III. Blood plasma Hcy and urinary SAM and SAM/SAH correlated with mortality, but plasma Hcy concentrations were more significant. Thus, plasma Hcy, urine SAM, and SAM/SAH can be considered to be potential diagnostic and prognostic markers in patients with CKD. Full article

The development of safe, orally available, and effective prophylactic countermeasures to protect our warfighters is an unmet need because there is no such FDA-approved countermeasure available for use. Th 1-Propanethiol, 3-(methylamino)-2-((methylamino)methyl) (PrC-210), a synthetic small molecule, is a member of a new family of aminothiols designed to reduce toxicity while scavenging reactive oxygen species (ROS). Our study investigated the protective role of a single oral administration of PrC-210 against radiation-induced hematopoietic and intestinal injury in mice. Pre-treatment with PrC-210 significantly improved the survival of mice exposed to a lethal dose of radiation. Our findings indicated that the radioprotective properties of PrC-210 are achieved by accelerating the recovery of the hematopoietic system, stimulating bone marrow progenitor cells, and ameliorating additional biomarkers of hematopoietic injury. PrC-210 pre-treatment reduced intestinal injury in mice exposed to a lethal dose of radiation by restoring jejunal crypts and villi, reducing translocation of bacteria to the spleen, maintaining citrulline levels, and reducing the sepsis marker serum amyloid A (SAA) in serum. Finally, PrC-210 pre-treatment led to a significant reduction (~10 fold) of Nos2 expression (inducible nitric oxide) in the spleen and decreased oxidative stress by enhancing the antioxidant defense system. These data support the further development of PrC-210 to receive approval from the FDA to protect warfighters and first responders from exposure to the harmful effects of ionizing radiation. Full article

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. Full article

Coronary artery disease (CAD) and the coronary artery bypass graft (CABG) are associated with a decreased blood glutathione (bGSH) level. Since GSH metabolism is closely related to other aminothiols (homocysteine and cysteine) and glucose, the aim of this study was to reveal the associations of bGSH with glucose and plasma aminothiols in CAD patients (N = 35) before CABG and in the early postoperative period. Forty-three volunteers with no history of cardiovascular disease formed the control group. bGSH and its redox status were significantly lower in CAD patients at admission. CABG had no significant effect on these parameters, with the exception of an increase in the bGSH/hemoglobin ratio. At admission, CAD patients were characterized by negative associations of homocysteine and cysteine with bGSH. All these associations disappeared after CABG. An association was found between an increase in oxidized GSH in the blood in the postoperative period and fasting glucose levels. Thus, CAD is associated with the depletion of the intracellular pool and the redox status of bGSH, in which hyperhomocysteinemia and a decrease in the bioavailability of the extracellular pool of cysteine play a role. The present study indicates that CABG causes disruptions in aminothiol metabolism and induces the synthesis of bGSH. Moreover, glucose becomes an important factor in the dysregulation of GSH metabolism in CABG. Full article

The multiplicity of simple molecules available on the primitive Earth probably made possible the development of extremely diverse prebiotic chemistry. The importance of thiols is widely recognized in the community studying the origin of life. De Duve’s “thioester world” has been considered a major contribution in this regard, where thioester bonds have high energies and thus can contribute to several chemical reactions. Herein, we propose specific models of thiols that exhibit unique activities toward several chemical reactions. Thanks to aminothiol and aminonitrile behaviors, we were able to obtain thiol-rich peptides with interesting catalytic activities leading to the formation of structurally diverse molecules. In a broader context, such chemistry could be introduced into systems chemistry scenarios in which it would be associated with the chemistry of nucleic acids or their precursors, as well as that of fatty acids. Full article

Radiation exposure can immediately trigger a burst of reactive oxygen species (ROS), which can induce severe cell death and long-term tissue damage. Therefore, instantaneous release of sufficient radioprotective drugs is vital to neutralize those accumulated ROS in IR-exposed areas. To achieve this goal, we designed, synthesized, and evaluated a novel oral ROS-responsive radioprotective compound (M1) with high biocompatibility and efficient ROS-scavenging ability to act as a promising oral drug for radiation protection. The compound is stably present in acidic environments and is hydrolyzed in the intestine to form active molecules rich in thiols. M1 can significantly remove cellular ROS and reduce DNA damage induced by γ-ray radiation. An in vivo experiment showed that oral administration of M1 effectively alleviates acute radiation-induced intestinal injury. Immunohistochemical staining showed that M1 improved cell proliferation, reduced cell apoptosis, and enhanced the epithelial integrity of intestinal crypts. This study provides a promising oral ROS-sensitive agent for acute intestinal radiation syndrome. Full article

Determination of oxyanions is of paramount importance because of the essential role they play in metabolic processes involved in various aquatic environmental problems. In this investigation, a novel chemical sensor array has been developed by using gold nanoparticles modified with different chain lengths of aminothiols (AET-AuNPs) as sensing elements. The proposed sensor array provides a fingerprint-like response pattern originating from cross-reactive binding events and capable of targeting various anions, including the herbicide glyphosate. In addition, chemometric techniques, linear discrimination analysis (LDA) and the support vector machine (SVM) algorithm were employed for analyte classification and regression/prediction. The obtained sensor array demonstrates a remarkable ability to determine multiple oxyanions in both qualitative and quantitative analysis. The described methodology could be used as a simple, sensitive and fast routine analysis for oxyanions in both laboratory and field settings. Full article

High-altitude locations are fascinating for investigating biological and physiological responses in humans. In this work, we studied the high-altitude response in the plasma and urine of six healthy adult trekkers, who participated in a trek in Nepal that covered 300 km in 19 days along a route in the Kanchenjunga Mountain and up to a maximum altitude of 5140 m. Post-trek results showed an unbalance in redox status, with an upregulation of ROS (+19%), NOx (+28%), neopterin (+50%), and pro-inflammatory prostanoids, such as PGE₂ (+120%) and 15-deoxy-delta12,14-PGJ₂ (+233%). The isoprostane 15-F_2t-IsoP was associated with low levels of TAC (−18%), amino-thiols, omega-3 PUFAs, and anti-inflammatory CYP450 EPA-derived mediators, such as DiHETEs. The deterioration of antioxidant systems paves the way to the overload of redox and inflammative markers, as triggered by the combined physical and hypoxic stressors. Our data underline the link between oxidative stress and inflammation, which is related to the concept of OxInflammation into the altitude hypoxia fashion. Full article

Background: Standard treatment of epileptic seizures involves the use of antiepileptic drugs (AEDs). Both AEDs themselves and treatment duration may influence the levels of biochemical parameters, e.g., lipids or homocysteine (HCys), that may increase the risk of cardiovascular diseases. The aim of the present study was to compare the levels of lipid parameters, as well as the concentrations of selected aminothiols (i.e., HCys, cysteine, and glutathione) between epileptic children treated with multiple AEDs and children without epilepsy. Methods: In the study, 21 children with epilepsy treated with two or more AEDs for at least 6 months (8 girls and 13 boys, mean age 7.03 ± 4.51) and 23 children without epilepsy (7 girls and 16 boys, mean age 7.54 ± 3.90) were prospectively analyzed. Lipid parameters, i.e., total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL), and levels of selected aminothiols were determined in the blood serum. Results: No differences in the mean levels of lipid parameters and in the mean values of lipid ratios (TC/HDL, TG/HDL, LDL/HDL) were observed between the total groups as well as in the sex subgroups. HCys and cysteine levels did not differ between the patients and controls. We observed significantly lower levels of glutathione in children with epilepsy than in children without epilepsy (1.49 ± 0.35 µmol/L vs. 2.39 ± 1.17 µmol/L, respectively) (p < 0.001). Glutathione level was also lower in boys with epilepsy than in boys without epilepsy (p = 0.007). Similarly, epileptic girls had statistically decreased levels of glutathione when compared to girls without epilepsy (p = 0.006). Conclusions: A lower level of glutathione is observed in pediatric patients with epilepsy treated with two or more AEDs for at least 6 months. This indicates the oxidative stress of the patients treated with AEDs, which in turn may affect their well-being, and in the case of chronic occurrence resulting from long-term treatment, also on the function of the liver and the condition of the cardiovascular system. Full article

The ongoing pandemic of coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), needs better treatment options both at antiviral and anti-inflammatory levels. It has been demonstrated that the aminothiol cysteamine, an already human applied drug, and its disulfide product of oxidation, cystamine, have anti-infective properties targeting viruses, bacteria, and parasites. To determine whether these compounds exert antiviral effects against SARS-CoV-2, we used different in vitro viral infected cell-based assays. Moreover, since cysteamine has also immune-modulatory activity, we investigated its ability to modulate SARS-CoV-2-specific immune response in vitro in blood samples from COVID-19 patients. We found that cysteamine and cystamine decreased SARS-CoV-2-induced cytopathic effects (CPE) in Vero E6 cells. Interestingly, the antiviral action was independent of the treatment time respect to SARS-CoV-2 infection. Moreover, cysteamine and cystamine significantly decreased viral production in Vero E6 and Calu-3 cells. Finally, cysteamine and cystamine have an anti-inflammatory effect, as they significantly decrease the SARS-CoV-2 specific IFN-γ production in vitro in blood samples from COVID-19 patients. Overall, our findings suggest that cysteamine and cystamine exert direct antiviral actions against SARS-CoV-2 and have in vitro immunomodulatory effects, thus providing a rational to test these compounds as a novel therapy for COVID-19. Full article

Exercise generates reactive oxygen species (ROS), creating a redox imbalance towards oxidation when inadequately intense. Normobaric and hyperbaric oxygen (HBO) breathed while not exercising induces antioxidant enzymes expression, but literature is still poor. Twenty-two athletes were assigned to five groups: controls; 30%, or 50% O₂; 100% O₂ (HBO) at 1.5 or 2.5 atmosphere absolute (ATA). Twenty treatments were administered on non-training days. Biological samples were collected at T0 (baseline), T1 (end of treatments), and T2 (1 month after) to assess ROS, antioxidant capacity (TAC), lipid peroxidation, redox (amino-thiols) and inflammatory (IL-6, 10, TNF-α) status, renal function (i.e., neopterin), miRNA, and hemoglobin. At T1, O₂ mixtures and HBO induced an increase of ROS, lipid peroxidation and decreased TAC, counterbalanced at T2. Furthermore, 50% O₂ and HBO treatments determined a reduced state in T2. Neopterin concentration increased at T1 breathing 50% O₂ and HBO at 2.5 ATA. The results suggest that 50% O₂ treatment determined a reduced state in T2; HBO at 1.5 and 2.5 ATA similarly induced protective mechanisms against ROS, despite the latter could expose the body to higher ROS levels and neopterin concentrations. HBO resulted in increased Hb levels and contributed to immunomodulation by regulating interleukin and miRNA expression. Full article