Nanomedicine for treating post-viral infectious disease syndrome is at an emerging stage. Despite promising results from preclinical studies on conventional antioxidants, their clinical translation as a therapy for treating post-COVID conditions remains challenging. The limitations are due to their low bioavailability, instability, limited transport to the target tissues, and short half-life, requiring frequent and high doses. Activating the immune system during coronavirus (SARS-CoV-2) infection can lead to increased production of reactive oxygen species (ROS), depleted antioxidant reserve, and finally, oxidative stress and neuroinflammation. To tackle this problem, we developed an antioxidant nanotherapy based on lipid (vesicular and cubosomal types) nanoparticles (LNPs) co-encapsulating ginkgolide B and quercetin. The antioxidant-loaded nanocarriers were prepared by a self-assembly method via hydration of a lyophilized mixed thin lipid film. We evaluated the LNPs in a new in vitro model for studying neuronal dysfunction caused by oxidative stress in coronavirus infection. We examined the key downstream signaling pathways that are triggered in response to potassium persulfate (KPS) causing oxidative stress-mediated neurotoxicity. Treatment of neuronally-derived cells (SH-SY5Y) with KPS (50 mM) for 30 min markedly increased mitochondrial dysfunction while depleting the levels of both glutathione peroxidase (GSH-Px) and tyrosine hydroxylase (TH). This led to the sequential activation of apoptotic and necrotic cell death processes, which corroborates with the crucial implication of the two proteins (GSH-Px and TH) in the long-COVID syndrome. Nanomedicine-mediated treatment with ginkgolide B-loaded cubosomes and vesicular LNPs showed minimal cytotoxicity and completely attenuated the KPS-induced cell death process, decreasing apoptosis from 32.6% (KPS) to 19.0% (MO-GB), 12.8% (MO-GB-Quer), 14.8% (DMPC-PEG-GB), and 23.6% (DMPC-PEG-GB-Quer) via free radical scavenging and replenished GSH-Px levels. These findings indicated that GB-LNPs-based nanomedicines may protect against KPS-induced apoptosis by regulating intracellular redox homeostasis.
- MeSH
- antioxidancia * farmakologie MeSH
- COVID-19 metabolismus MeSH
- farmakoterapie COVID-19 * MeSH
- ginkgolidy * farmakologie MeSH
- glutathionperoxidasa * metabolismus MeSH
- laktony farmakologie MeSH
- lidé MeSH
- nanočástice * MeSH
- nanomedicína * metody MeSH
- neurony účinky léků virologie MeSH
- oxidační stres * účinky léků MeSH
- quercetin farmakologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- SARS-CoV-2 účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Pollution with heavy metal salts is an important environmental problem today, having an adverse effect on public health. The endocrine system maintains homeostasis in the body. The antioxidant protection (GPX-1) of the pineal gland in mature rats was studied. Animals of the experimental group represented a model of microelementosis, achieved by adding a mixture of heavy metal salts for 90 days to drinking water: zinc (ZnSO4×7H2O) - 5 mg/l, copper (CuSO4×5H2O) - 1 mg/l, iron (FeSO4) - 10 mg/l, manganese (MnSO4×5H2O) - 0.1 mg/l, lead (Pb(NO3)2) - 0.1 mg/l, and chromium (K2Cr2O7) - 0.1 mg/l. Morphological, statistical and immunohistochemical (GPX-1) research methods were used. Long-term (90-days) intake of heavy metal salts mixture in the body of experimental animals brought about development of the general adaptation syndrome, the stage of chronic stress "subcompensation" in the pineal gland. Morphological rearrangements were of nonspecific polymorphic nature as severe hemodynamics disorder in the organ, impairment of vascular wall morphology, development of tissue hypoxia and oxidative stress, accompanied by processes of accelerated apoptosis in part of pinealocytes, by a significant decrease in glutathione peroxidase level in the organ and reactive astrogliosis as a response to the damaging agent's action. Along with the negative changes in the pineal gland, a compensatory-adaptive processes with signs of functional stress also occurred. A sufficiently high degree of glutathione peroxidase activity in 39% of pinealocytes located perivascularly, active adaptive glial reaction and activation of synthetic processes in some pinealocytes were also observed.
- MeSH
- epifýza mozková * MeSH
- glutathionperoxidasa MeSH
- krysa rodu rattus MeSH
- soli MeSH
- těžké kovy * toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In the rat model, 6-hydroxydopamine (6-OHDA) known as a selective catecholaminergic neurotoxin used chiefly in modeling Parkinson's disease (PD). Continuous aerobic exercise and curcumin supplementations could play a vital role in neuroprotection. This study aimed to explore the neuroprotective roles of regular aerobic exercise and curcumin during PD. For this, rats were treated as follows for 8 consecutive weeks (5 d in a week): For this, animals were orally treated with curcumin (50 ml/kg) alone or in combination with aerobic exercise. Compared with a control group, induction of PD by 6-OHDA increased the amount of alpha-synuclein protein and malondialdehyde levels and decreased the number of substantia nigra neurons, total antioxidant capacity, and glutathione peroxidase activity in brain tissue. All these changes were abolished by the administration of curcumin with aerobic exercise treatments. Activity behavioral tests also confirmed the above-mentioned results by increasing the rod test time and the number of rotations due to apomorphine injection. Histopathology assays mimic the antioxidant activity and behavioral observations. Combined curcumin with aerobic exercise treatments is potentially an effective strategy for modifying the dopaminergic neuron dysfunction in 6-OHDA-induced rats modeling PD via dual inhibiting oxidative stress indices and regulating behavioral tasks.
- MeSH
- alfa-synuklein metabolismus MeSH
- antioxidancia metabolismus farmakologie MeSH
- apomorfin metabolismus farmakologie MeSH
- glutathionperoxidasa metabolismus MeSH
- krysa rodu rattus MeSH
- kurkumin * metabolismus farmakologie MeSH
- malondialdehyd MeSH
- modely nemocí na zvířatech MeSH
- neuroprotektivní látky * farmakologie MeSH
- neurotoxické syndromy * MeSH
- neurotoxiny metabolismus farmakologie MeSH
- oxidopamin toxicita MeSH
- Parkinsonova nemoc * farmakoterapie metabolismus MeSH
- substantia nigra MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Ferroptosis is a recently described programmed cell death mechanism that is characterized by the buildup of iron (Fe)-dependent lipid peroxides in cells and is morphologically, biochemically, and genetically distinct from other forms of cell death, having emerged to play an important role in cancer biology. Ferroptosis has significant importance during cancer treatment because of the combination of factors, including suppression of the glutathione peroxidase 4 (Gpx4), cysteine deficiency, and arachidonoyl (AA) peroxidation, which cause cells to undergo ferroptosis. However, the physiological significance of ferroptosis throughout development is still not fully understood. This current review is focused on the factors and molecular mechanisms with the diagrammatic illustrations of ferroptosis that have a role in the initiation and sensitivity of ferroptosis in various malignancies. This knowledge will open a new road for research in oncology and cancer management.
- MeSH
- ferroptóza * MeSH
- fosfolipidová hydroperoxidglutathionperoxidasa MeSH
- lidé MeSH
- lipidové peroxidy MeSH
- nádory * farmakoterapie metabolismus MeSH
- peroxidace lipidů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: The inflammatory process in Crohn's disease (CD) is closely associated with the formation of reactive oxygen species. Antioxidant enzymes can play an important role in the outcome of CD and may influence postoperative recurrence in these patients. The aim of our study was to evaluate gene expression of intracellular antioxidant enzymes in surgically resected intestinal specimens of patients with CD, both in macroscopically normal and in inflamed tissue. METHODS: A total of 28 patients referred for elective bowel resection were enrolled in the study. Full-thickness small intestinal specimens were investigated. Gene expression of antioxidant enzymes - superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GSR) - was evaluated both in macroscopically normal and inflamed samples. RESULTS: There were significantly lower levels of SOD1 mRNA (p = 0.007) and GSR mRNA (p = 0.027) in inflamed tissue compared to macroscopically normal areas. No significant differences were found between affected and non-affected intestinal segments in mRNA for SOD2, SOD3 and GPX. CONCLUSIONS: Our pilot data clearly showed that the gene expression of major antioxidant enzymes is not a uniform mechanism in the pathogenesis of Crohn's disease. Topically decreased gene expression of SOD1 and GSR might facilitate the segmental tissue injury caused by reactive oxygen species.
- MeSH
- antioxidancia * MeSH
- Crohnova nemoc * genetika metabolismus MeSH
- exprese genu * MeSH
- glutathionperoxidasa genetika MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- reaktivní formy kyslíku MeSH
- střeva MeSH
- superoxid dismutáza 1 * genetika metabolismus MeSH
- superoxiddismutasa genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Souvislosti a cíle: Záměrem této studie je objasnit vztah mezi úrovní oxidačního stresu (OS), depresí (D) a rizikem opakovaného výskytu stabilní ischemické choroby srdeční (sICHS). Metody: Retrospektivní studie se zúčastnilo 174 osob ve věku 45+: 86 hospitalizovaných pacientů kardiologického oddělení s rekurentní sICHS a 88 hospitalizovaných pacientů kardiologického oddělení s primární sICHS. Vážnost symptomů deprese byla hodnocena za použití 30bodového dotazníku Geriatrické škály deprese (GDS), platné lotyšské verze GDS-LAT. Každému pacientovi byly odebrány vzorky krve za účelem změření parametrů oxidačního stresu malondialdehydu (MDA) a glutathionu peroxidázy (GPx). Výsledky: 83,9 % vzorků mělo vysokou koncentraci MDA. V 72,4 % byl vzorek hodnoty GPx normální, v 17,8 % byla hodnota vysoká a v 9,8 % nízká. O něco více než polovina pacientů má depresi (44,3 % mírnou D a 6,9 % těžkou D). GPx se statisticky lišila u primární a rekurentní sICHS (p = 0,003). Pacienti s D a vysokým GPx měli 10,6krát vyšší pravděpodobnost opakované sICHS ve srovnání s pacienty bez D a s normální GPx (p = pacienti s D měli obě hodnoty MDA a GPx vysoké častěji než účastníci bez D, ale nebylo to statisticky významné [p = 0,51]). Závěr: V uvedené studii bylo zjištěno, že koncentrace antioxidačního (AO) enzymu GPx byla podstatně vyšší u depresivních pacientů s opakovanou sICHS ve srovnání s pacienty bez D a s pacienty s primární ICHS a pacienti s D i s vysokým GPx měli vyšší pravděpodobnost opakované sICHS ve srovnání s těmi bez D a s normálním GPx. Dá se předpokládat, že GPx je významnější marker rizika D a opakované sICHS. Koncentrace MDA ve většině z obou skupin (primární a opakovaná sICHS) pacientů by mohla dokazovat, že zvýšená koncentrace OS je všeobecně rizikový faktor ischemické choroby srdeční. Monitorování biomarkerů OS se zdá být významné ve zvládání komorbidity sICHS s D. Bylo by vhodné provést další studie, které by potvrdily tyto nálezy.
Aim: The aim of the study was to investigate the relationships between a level of oxidative stress (OS), depression (D) and risk of recurrence of stable coronary heart disease (SCHD). Methods: A retrospective study was conducted on 174 participants, at the age 45+ years: 86 in-patients of the cardiology department with a recurrent SCHD and 88 in-patients of the cardiology department with primary SCHD. The severity of depressive symptoms was assessed using the long 30-item form of Geriatric Depression Scale (GDS), valid Latvian version of GDS-LAT. The blood samples were taken from each patient to measure oxidative stress parameters malondialdehyde (MDA) and glutathione peroxidase (GPx). Results: 83.9% of the sample had high level of MDA. In 72.4% of the sample the GPx level was normal, in 17.8% it was high and in 9.8% low. Slightly more than a half of the patients were experiencing depression (44.3% - mild D and 6.9% - severe D). GPx was found statistically differing between primary and recurrent SCHD (p = 0,003). Patients with both D and high GPx had 10.6 times higher chances of recurrent SHCD compared to those without D and normal GPx (p = patients with present D were experiencing both - high levels of MDA and GPx - more often than responders with no D, but this wasn't statistically signifi cant [p = 0.51]). Conclusion: In the present study it was found that level of antioxidant (AO) enzyme GPx was signifi cantly higher in depressed patients with recurrent SCHD compared to patients without D and to patients with primary SCHD and patients with both D and high GPx had higher chances of recurrent SCHD compared to those without D and normal GPx. It could be supposed that GPx is a more signifi cant marker of risk of D and recurrence of SCHD. The high level of MDA in most of both (primary and recurrent SCHD) groups patients could evidence that increased OS is a risk factor for CHD in general. Monitoring OS biomarkers seems to be important in the management of SCHD comorbidity with D. Further studies are warranted to confi rm these findings.
- MeSH
- biologické markery MeSH
- deprese MeSH
- glutathionperoxidasa krev MeSH
- hematologické testy MeSH
- koronární nemoc * etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- malondialdehyd krev MeSH
- oxidační stres MeSH
- psychiatrické posuzovací škály MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- rizikové faktory kardiovaskulárních chorob * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spektrofotometrie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
Oxidative status has been proposed as an important ecological and evolutionary force given that pro-oxidant metabolites damage molecules, cells and tissues, with fitness consequences for organisms. Consequently, organisms usually face a trade-off between regulating their oxidative status and other physiological traits. However, environmental stressors and the availability of dietary-derived antioxidants vary according to local conditions and, thus, organisms inhabiting different habitats face different oxidative pressures. Still, there is little information on how different environmental conditions influence the oxidative status of animals inhabiting terrestrial environments. In this work, we examined the variation in oxidative status in the blue tit (Cyanistes caeruleus), a bird species with hatching asynchrony. Specifically, we examined the oxidative status of the largest and the smallest nestlings in the brood, inhabiting four forests differing in food availability and ectoparasite prevalence. We measured lipid peroxidation (malondialdehyde; MDA) as a marker of oxidative damage, total antioxidant capacity (Trolox-equivalent antioxidant capacity; TEAC) and antioxidant enzymatic activity (catalase, glutathione S-transferase, glutathione peroxidase) in blood samples. The glutathione peroxidase (GPX) activity differed among the forests, being the highest in the pine forest and the lowest in a mixed oak (Quercus) forest in the most humid area. Lipid peroxidation was higher in larger nestlings, suggesting higher oxidative damage with an increasing growth rate. Neither brood size, laying date, nor ectoparasites were related to the oxidative status of nestlings. These results suggest that nest rearing conditions might shape the oxidative status of birds, having consequences for habitat-dependent variation in regulation of oxidative status.
- MeSH
- antioxidancia metabolismus MeSH
- dieta * MeSH
- ekosystém * MeSH
- glutathionperoxidasa metabolismus MeSH
- katalasa metabolismus MeSH
- malondialdehyd metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres fyziologie MeSH
- Passeriformes fyziologie MeSH
- peroxidace lipidů MeSH
- zeměpis MeSH
- zpěvní ptáci fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Španělsko MeSH
To investigate the effect of vanadyl trehalose (VT) on oxidative stress and reduced glutathione/glutathione-S-transferase (GSH/GSTs) pathway gene expression in mouse gastrointestinal tract, as well as the protective effects of vitamin C (VC) and reduced glutathione (GSH). Thirty male Kunming mice were randomly divided into five groups: control group (group A), VT group (group B), VC + VT group (group C), GSH + VT group (group D) and VC + GSH + VT group (group E). The content of reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) activity and the expressions of glutamate-cysteine ligase catalytic subunit (GCLC), glutathione synthetase (GSS), regulated through glutathione reductase (GSR) and glutathione-S-transferase pi (GSTpi) in stomach and duodenum in vanadyl trehalose treated group were lower than those in group A (P<0.05). The C, D, E group can significantly improve the above indicators, but those only in the stomach in E group reached the level of the control group. Vanadyl trehalose (VT) was able to cause oxidative stress damage to the gastrointestinal tract of mice, which affects GSH content and GSH-Px activity and interferes with the normal expression of GSH/GSTs pathway. Exogenous vitamin C, reduced glutathione and the combination of the two could play a specific role in antioxidant protection and reduce the toxicity of vanadyl trehalose.
- MeSH
- antioxidancia farmakologie MeSH
- biomimetika MeSH
- glutathion metabolismus MeSH
- glutathionperoxidasa metabolismus MeSH
- glutathionreduktasa metabolismus MeSH
- glutathiontransferasa metabolismus MeSH
- hypoglykemika farmakologie MeSH
- inzulin farmakologie MeSH
- kyselina askorbová farmakologie MeSH
- myši MeSH
- oxidační stres MeSH
- trehalosa farmakologie MeSH
- vanadáty farmakologie MeSH
- žaludek účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.
- MeSH
- aerobióza MeSH
- antioxidancia metabolismus MeSH
- centrální nervový systém metabolismus MeSH
- dítě MeSH
- dysbióza komplikace MeSH
- gastrointestinální nemoci komplikace MeSH
- glutathionperoxidasa metabolismus MeSH
- incidence MeSH
- lidé MeSH
- metalothionein metabolismus MeSH
- mitochondrie metabolismus MeSH
- mozek - chemie MeSH
- neurodegenerativní nemoci etiologie metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres * MeSH
- peroxidace lipidů MeSH
- poruchy autistického spektra epidemiologie imunologie metabolismus patofyziologie MeSH
- předškolní dítě MeSH
- scavengery volných radikálů metabolismus MeSH
- selen fyziologie MeSH
- selenoproteiny metabolismus MeSH
- střevní mikroflóra MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Oxidative stress and decline in cellular redox regulation have been hypothesized to play a key role in cardiovascular aging; however, data on antioxidant and redox regulating systems in the aging heart are controversial. The aim of the present study was to examine the effect of aging on critical antioxidant enzymes and two major redox-regulatory systems glutathione (GSH) and thioredoxin (Trx) system in hearts from adult (6-month-old), old (15-month-old), and senescent (26-month-old) rats. Aging was associated with a non-uniform array of changes, including decline in contents of reduced GSH and total mercaptans in the senescent heart. The activities of Mn-superoxide dismutase (SOD2), glutathione peroxidase (GPx), glutathione reductase (GR), and thioredoxin reductase (TrxR) exhibited an age-related decline, whereas catalase was unchanged and Cu,Zn-superoxide dismutase (SOD1) displayed only slight decrease in old heart and was unchanged in the senescent heart. GR, Trx, and peroxiredoxin levels were significantly reduced in old and/or senescent hearts, indicating a diminished expression of these proteins. In contrast, SOD2 level was unchanged in the old heart and was slightly elevated in the senescent heart. Decline in GPx activity was accompanied by a loss of GPx level only in old rats, the level in senescent heart was unchanged. These results indicate age-related posttranslational protein modification of SOD2 and GPx. In summary, our data suggest that changes are more pronounced in senescent than in old rat hearts and support the view that aging is associated with disturbed redox balance that could alter cellular signaling and regulation.
- MeSH
- antioxidancia analýza metabolismus MeSH
- glutathionperoxidasa analýza metabolismus MeSH
- krysa rodu rattus MeSH
- myokard chemie enzymologie MeSH
- oxidace-redukce MeSH
- potkani Wistar MeSH
- stárnutí metabolismus MeSH
- superoxiddismutasa metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
