Ferroptosis, a form of regulated cell death (RCD) with unique morphological and biochemical features, has potential in cancer treatment. In this study, erastin (ER)-induced ferroptosis was investigated in cancer cell lines A549, Calu1, and K562. A detailed analysis of the Xc-/GSH/GPX4 axis showed that glutathione (GSH) production, unlike GPX4 expression, is an important factor in influencing the sensitivity of tumor cells to ER despite oncogenic KRAS expression. Here we show for the first time that ferroptosis is associated with marked condensation of cell nuclei, a morphological change that was previously associated exclusively with apoptosis. Importantly, this phenomenon was observed in all three cell lines. Further, thiourea (TU), a known scavenger of reactive oxygen species (ROS) had a complex effect on ER induced ferroptosis. While TU significantly potentiated ER cytotoxicity and changed the mode of cell death from ferroptotic to apoptotic in A549 and K562 cells, it had a mild protective effect in Calu1 cells without changing the mode of cell death. In conclusion, the results show that Xc--dependent GHS production affects the sensitivity of oncogenic RAS-expressing tumor cells to ER treatment. ER-induced ferroptosis is associated with nuclear condensation. Further, we identified TU as a compound that can change the form of cell death from ferroptotic to apoptotic in some cancer cells. The latter two findings suggest a previously uncovered proximity of the regulatory pathways of ferroptosis and apoptosis.

• Klíčová slova
• Apoptosis, Chromatin condensation, Erastin, Ferroptosis, Thiourea,
• MeSH
• apoptóza účinky léků   MeSH
• buňky K562 MeSH
• ferroptóza * účinky léků   MeSH
• fosfolipidová hydroperoxidglutathionperoxidasa metabolismus   MeSH
• glutathion metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory patologie   metabolismus   MeSH
• piperaziny * farmakologie   MeSH
• protinádorové látky * farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• thiomočovina farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• erastin MeSH Prohlížeč
• fosfolipidová hydroperoxidglutathionperoxidasa MeSH
• glutathion MeSH
• piperaziny * MeSH
• protinádorové látky * MeSH
• reaktivní formy kyslíku MeSH
• thiomočovina MeSH

Cross-linked poly(alkylene citates) (cPAC) based on 1,6-hexanediol (cPHC) and 1,8-octanediol (cPOC) and modified with 0.4, 0.8 and 1.6% w/w L-glutathione (GSH) were synthesized as potential materials for vascular tissue engineering. The materials prepared at a citric acid : diol molar ratio of 2 : 3 exhibited superior mechanical strength and reduced acidity in comparison to the 1 : 1 materials. All materials exhibited blue fluorescence, which intensity was enhanced with increasing GSH concentration. Conversely, the latter demonstrated marginally enhanced antioxidant properties. The preliminary cell culture tests of the 2 : 3 materials with human adipose tissue stem cells (ASCs) revealed that cPOC did not provide an appropriate environment for cell colonization due to its higher acidity than cPHC. In contrast, cPHC promoted the growth of ASCs and other cell types, including fibroblasts (NHDFs), endothelial cells (HUVECs), and smooth muscle cells (SMCs), at all GSH concentrations, with minimal negative effect on HUVEC and SMC proliferation. The induction of oxidative stress by menadione demonstrated a notable decline in the metabolic activity of both ASCs and NHDFs on cPHCs across all GSH concentrations. However, an incremental protective effect on the cells was observed with increasing GSH concentrations. In contrast, HUVECs and SMCs demonstrated increased metabolic activity, without the protective effect of GSH being observed. Therefore, the findings demonstrate that cell type-specific differences exist in cell response to oxidative stress. Consequently, the addition of antioxidants to the polymer should be guided by the intended cell type for use in vascular reconstruction. Our results also suggest an intrinsic antioxidant activity of cPHC materials and their good hemocompatibility with human blood in vitro.

• MeSH
• antioxidancia chemie   farmakologie   MeSH
• biokompatibilní materiály * chemie   farmakologie   chemická syntéza   MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• glutathion * chemie   farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• molekulární struktura MeSH
• myocyty hladké svaloviny cytologie   účinky léků   MeSH
• oxidační stres * účinky léků   MeSH
• polymery * chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• reagencia zkříženě vázaná chemie   MeSH
• tkáňové inženýrství * MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• biokompatibilní materiály * MeSH
• glutathion * MeSH
• polymery * MeSH
• reagencia zkříženě vázaná MeSH

The increasing occurrence of TiO2 nanoparticles in the environment leads to a higher risk of their entry into the human body. Because the nanomaterials can cross the blood-brain barrier, the knowledge of their effect in neural cells is also crucial. However, the exact mechanism of toxicity remains unclear. Therefore, our objective was to evaluate the biological effect of TiO2 nanoparticles in neural cells. Therefore, we aimed to evaluate the biological effect of TiO2 nanoparticles in neural cells. We used neuroblastoma SH-SY5Y cells treated with 25 nm TiO2 nanoparticles (TiO2 P25; 1-100 μg·mL-1; 24-72 h). We measured dehydrogenase activity, glutathione metabolism, DNA damage and mitochondrial respiration. After treatment of SH-SY5Y cells with TiO2 P25, we found a dose- and time-dependent decrease in dehydrogenase activity together with nuclear changes. Interestingly, 100 μg·mL-1 TiO2 P25 caused a significant increase of glutathione levels (p < 0.001) linked with increased glutamate-cysteine ligase expression after both 24 and 48 h. Furthermore, as the first study at all, we observed the significant decreases of mitochondrial respiration in SH-SY5Y cells caused by treatments with 10 and 100 μg·mL-1 TiO2 P25 after 48 and 72 h. In conclusion, our study brings new finding of occurrence of decreased mitochondrial respiration without glutathione depletion in SH-SY5Y cells contributing to the understanding of TiO2 P25 toxicity in neural cells.

• Klíčová slova
• Glutathione, Mitochondrial damage, Nanotoxicity, Neuronal cells, TiO(2) P25 nanoparticles,
• MeSH
• glutamátcysteinligasa metabolismus   MeSH
• glutathion * biosyntéza   metabolismus   MeSH
• kovové nanočástice * toxicita   MeSH
• lidé MeSH
• mitochondrie * účinky léků   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nanočástice * toxicita   MeSH
• neurony * účinky léků   metabolismus   MeSH
• poškození DNA účinky léků   MeSH
• titan * toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glutamátcysteinligasa MeSH
• glutathion * MeSH
• titan * MeSH
• titanium dioxide MeSH Prohlížeč

This study investigates the association between serum glutathione (GSH) and malondialdehyde (MDA) levels and early neurological deficits and short-term outcomes in individuals with acute cerebral infarction (ACI). The study included 114 patients with ACI within 48 hours of symptom onset, between January and August 2023, alongside 96 healthy individuals as a control group. Neurological deficits were assessed using the National Institute of Health Stroke Scale (NIHSS), classifying deficits as mild (<5) or moderate to severe (>/=5). Associations between GSH and MDA levels with early neurological deficits were analyzed. Short-term prognosis, assessed three months post-discharge using the Modified Rankin Scale (mRS), was examined in relation to GSH and MDA levels in patients with ACI. Independent predictors of neurological deficits and short-term outcomes were identified through binary logistic regression analysis. Compared to the control group, patients with ACI had higher rates of hypertension, diabetes, smoking, and alcohol consumption. Additionally, elevated levels of MDA, glycated hemoglobin, triglycerides, C-reactive protein (CRP), and D-dimer levels were observed, whereas GSH and high-density lipoprotein (HDL) levels were lower. Among those with moderate to severe ACI, levels of CRP, MDA, triglycerides, low-density lipoprotein (LDL), uric acid, and D-dimer levels were higher compared to mild ACI, while HDL and GSH levels were significantly lower. Low serum GSH levels and elevated MDA levels are associated with early neurological deficits and short-term prognosis in ACI, serving as independent risk factors for adverse prognosis. The combined assessment of MDA, infarct volume, and LDL provides enhanced predictive value for adverse prognosis in patients with ACI. Keywords: Acute cerebral infarction, Malondialdehyde, Neurological deficits, Serum glutathione, Short-term prognosis.

• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• cerebrální infarkt * krev   diagnóza   komplikace   MeSH
• glutathion * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malondialdehyd * krev   MeSH
• nemoci nervového systému * krev   diagnóza   etiologie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• glutathion * MeSH
• malondialdehyd * MeSH

Skin represents the largest organ in the human body, functioning as a protective barrier against environmental factors while playing a critical role in thermoregulation. Acne vulgaris is recognized as the most common dermatological condition affecting adolescents, and if left untreated, it can result in lasting skin damage and associated psychosocial challenges. This study aims to develop innovative polymeric biomaterials that could effectively support the treatment of acne vulgaris. The synthesis of these biomaterials involves the use of polyethylene glycol 6000, sodium alginate, and the antioxidant protein glutathione (GHS) to create polymeric hydrogels. These hydrogels were generated via a UV-mediated crosslinking process. To enhance the functional properties of the hydrogels, zinc oxide microparticles (ZnO), synthesized through a wet precipitation method, were incorporated into the formulations. Characterization of the ZnO was performed using Fourier-Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), particle sizer analysis, and Scanning Electron Microscopy (SEM). Additionally, the bioactivity of the synthesized materials was evaluated through incubation in media simulating physiological body fluids. The cytotoxic effects of the biomaterials were assessed using an indirect test on mouse fibroblast (L929) cells, in accordance with ISO 10993-5 guidelines. The results of our research indicate that the developed biomaterials exhibit potential as a carrier for active substances, contributing positively to the treatment of acne vulgaris and potentially improving overall skin health.

• Klíčová slova
• acne vulgaris, active substance carrier, hydrogels, polyethylene glycol, sodium alginate, zinc oxide microparticles,
• MeSH
• buněčné linie MeSH
• fibroblasty účinky léků   MeSH
• glutathion * chemie   farmakologie   MeSH
• hydrogely * chemie   farmakologie   MeSH
• kůže * účinky léků   MeSH
• lidé MeSH
• myši MeSH
• nosiče léků * chemie   MeSH
• oxid zinečnatý * chemie   farmakologie   MeSH
• regenerace * účinky léků   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glutathion * MeSH
• hydrogely * MeSH
• nosiče léků * MeSH
• oxid zinečnatý * MeSH

OBJECTIVES: To evaluate the effect of short-term inhalational exposure to nanoparticles released during dental composite grinding on oxidative stress and antioxidant capacity markers. MATERIALS AND METHODS: Twenty-four healthy volunteers were examined before and after exposure in dental workshop. They spent 76.8 ± 0.7 min in the testing room during grinding of dental nanocomposites. The individual exposure to aerosol particles in each participant´s breathing zones was monitored using a personal nanoparticle sampler (PENS). Exhaled breath condensate (EBC), blood, and urine samples were collected pre- and post-exposure to measure one oxidative stress marker, i.e., thiobarbituric acid reactive substances (TBARS), and two biomarkers of antioxidant capacity, i.e., ferric-reducing antioxidant power (FRAP) and reduced glutathione (GSH) by spectrophotometry. Spirometry and fractional exhaled nitric oxide (FeNO) were used to evaluate the effect of acute inhalational exposure. RESULTS: Mean mass of dental nanocomposite ground away was 0.88 ± 0.32 g. Average individual doses of respirable particles and nanoparticles measured by PENS were 380 ± 150 and 3.3 ± 1.3 μg, respectively. No significant increase of the post-exposure oxidative stress marker TBARS in EBC and plasma was seen. No decrease in antioxidant capacity biomarkers FRAP and GSH in EBC post-exposure was seen, either. Post-exposure, conjunctival hyperemia was seen in 62.5% volunteers; however, no impairment in spirometry or FeNO results was observed. No correlation of any biomarker measured with individual exposure was found, however, several correlations with interfering factors (age, body mass index, hypertension, dyslipidemia, and environmental pollution parameters) were seen. CONCLUSIONS: This study, using oxidative stress biomarker and antioxidant capacity biomarkers in biological fluids of volunteers during the grinding of dental nanocomposites did not prove a negative effect of this intense short-term exposure. However, further studies are needed to evaluate oxidative stress in long-term exposure of both stomatologists and patients and diverse populations with varying health statuses.

• Klíčová slova
• Dental nanocomposite, Exhaled airway markers, Nanoparticles, Occupational lung disease, Respiratory function test,
• MeSH
• antioxidancia analýza   MeSH
• biologické markery analýza   MeSH
• dechové testy MeSH
• dospělí MeSH
• glutathion MeSH
• inhalační expozice * škodlivé účinky   MeSH
• látky reagující s kyselinou thiobarbiturovou analýza   MeSH
• lidé MeSH
• mladý dospělý MeSH
• nanočástice škodlivé účinky   MeSH
• nanokompozity * škodlivé účinky   MeSH
• oxid dusnatý analýza   MeSH
• oxidační stres MeSH
• pracovní expozice * škodlivé účinky   MeSH
• zubní lékaři * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• biologické markery MeSH
• glutathion MeSH
• látky reagující s kyselinou thiobarbiturovou MeSH
• oxid dusnatý MeSH

Tumor cells often adapt to amino acid deprivation through metabolic rewiring, compensating for the loss with alternative amino acids/substrates. We have described such a scenario in leukemic cells treated with L-asparaginase (ASNase). Clinical effect of ASNase is based on nutrient stress achieved by its dual enzymatic action which leads to depletion of asparagine and glutamine and is accompanied with elevated aspartate and glutamate concentrations in serum of acute lymphoblastic leukemia patients. We showed that in these limited conditions glutamate uptake compensates for the loss of glutamine availability. Extracellular glutamate flux detection confirms its integration into the TCA cycle and its participation in nucleotide and glutathione synthesis. Importantly, it is glutamate-driven de novo synthesis of glutathione which is the essential metabolic pathway necessary for glutamate's pro-survival effect. In vivo findings support this effect by showing that inhibition of glutamate transporters enhances the therapeutic effect of ASNase. In summary, ASNase induces elevated extracellular glutamate levels under nutrient stress, which leads to a rewiring of intracellular glutamate metabolism and has a negative impact on ASNase treatment.

• MeSH
• akutní lymfatická leukemie farmakoterapie   metabolismus   patologie   MeSH
• asparaginasa * farmakologie   metabolismus   MeSH
• citrátový cyklus účinky léků   MeSH
• glutamin metabolismus   MeSH
• glutathion * metabolismus   MeSH
• kyselina glutamová * metabolismus   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• protinádorové látky farmakologie   MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• asparaginasa * MeSH
• glutamin MeSH
• glutathion * MeSH
• kyselina glutamová * MeSH
• protinádorové látky MeSH

Redox regulations and antioxidant defence play a central role in the acclimation of plants to their environment. Glutathione represents an essential component of the cellular antioxidant defence system, which keeps levels of reactive oxygen species (ROS) under control. High-performance liquid chromatography (HPLC) separation with fluorescence detection is a sensitive method that enables analysis of reduced and oxidised glutathione levels in small samples of plant tissues or plant cell culture. We aimed to optimise the method to obtain more accurate information about the total level of glutathione and the proportion of the reduced form (GSH) by choosing the most suitable reduction reagent and the conditions under which the reduction occurs. The applicability of the developed method was verified by analysing tobacco cells treated with hydrogen peroxide, which caused a decrease in the GSH/total glutathione ratio. Significant changes in the level of glutathione as well as in the GSH/total glutathione ratio were also observed during tobacco cell culture development.

• Klíčová slova
• Glutathione, HPLC analysis, Monochlorobimane reagent, Nicotiana tabacum, tris(2-carboxyethyl)phosphine,
• MeSH
• glutathion * analýza   MeSH
• kalibrace MeSH
• kultivované buňky MeSH
• oxidace-redukce MeSH
• oxidační stres * MeSH
• peroxid vodíku farmakologie   MeSH
• rostlinné buňky * MeSH
• tabák * genetika   metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie * metody   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glutathion * MeSH
• peroxid vodíku MeSH

Cadmium crosses the blood-brain barrier inducing damage to neurons. Cell impairment is predominantly linked to oxidative stress and glutathione (GSH) depletion. On the other hand, several reports have described an increase of GSH levels in neuronal cells after CdCl2 exposure. Therefore, the aim of the present report was to investigate the relation between changes in GSH levels and mitochondrial damage in neuronal cells after CdCl2 treatment. To characterize neuronal impairment after CdCl2 treatment (0-200 μM) for 1-48 h, we used the SH-SY5Y cell line. We analyzed GSH metabolism and determined mitochondrial activity using high-resolution respirometry. CdCl2 treatment induced both the decreases and increases of GSH levels in SH-SY5Y cells. GSH concentration was significantly increased in cells incubated with up to 50 μM CdCl2 but only 100 μM CdCl2 induced GSH depletion linked to increased ROS production. The overexpression of proteins involved in GSH synthesis increased in response to 50 and 100 μM CdCl2 after 6 h. Finally, strong mitochondrial impairment was detected even in 50 μM CdCl2 treated cells after 24 h. We conclude that a significant decrease in mitochondrial activity can be observed in 50 μM CdCl2 even without the occurrence of GSH depletion in SH-SY5Y cells.

• Klíčová slova
• Cadmium toxicity, Glutathione depletion, Mitochondrial damage, Neuronal cells, Oxidative stress,
• MeSH
• chlorid kademnatý * toxicita   MeSH
• glutathion * metabolismus   MeSH
• lidé MeSH
• mitochondrie * účinky léků   metabolismus   MeSH
• nádorové buněčné linie MeSH
• neurony * účinky léků   metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chlorid kademnatý * MeSH
• glutathion * MeSH
• reaktivní formy kyslíku MeSH

Increased awareness of the impact of human activities on the environment has emerged in recent decades. One significant global environmental and human health issue is the development of materials that could potentially have negative effects. These materials can accumulate in the environment, infiltrate organisms, and move up the food chain, causing toxic effects at various levels. Therefore, it is crucial to assess materials comprising nano-scale particles due to the rapid expansion of nanotechnology. The aquatic environment, particularly vulnerable to waste pollution, demands attention. This review provides an overview of the behavior and fate of metallic nanoparticles (NPs) in the aquatic environment. It focuses on recent studies investigating the toxicity of different metallic NPs on aquatic organisms, with a specific emphasis on thiol-biomarkers of oxidative stress such as glutathione, thiol- and related-enzymes, and metallothionein. Additionally, the selection of suitable measurement methods for monitoring thiol-biomarkers in NPs' ecotoxicity assessments is discussed. The review also describes the analytical techniques employed for determining levels of oxidative stress biomarkers.

• Klíčová slova
• Aquatic organism, Glutathione, Mass spectrometry, Metallothionein, Oxidative stress,
• MeSH
• antioxidancia * metabolismus   MeSH
• biologické markery * metabolismus   MeSH
• chemické látky znečišťující vodu * toxicita   analýza   MeSH
• glutathion metabolismus   MeSH
• kovové nanočástice * toxicita   chemie   MeSH
• lidé MeSH
• metalothionein metabolismus   MeSH
• monitorování životního prostředí metody   MeSH
• oxidační stres * účinky léků   MeSH
• peptidy toxicita   MeSH
• vodní organismy účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia * MeSH
• biologické markery * MeSH
• chemické látky znečišťující vodu * MeSH
• glutathion MeSH
• metalothionein MeSH
• peptidy MeSH