Díky svému umístění chrání hydrofobní lipidová doména paraoxonázy-1 (PON-1) lipoproteiny o vysoké hustotě (high-density lipoprotein, HDL), lipoproteiny o nízké hustotě (low-density lipoprotein, LDL) a buněčné membrány na vnější straně před oxidací. Nezastavuje se tím tvorba konjugovaných dienů, ale mění se tak produkty lipoperoxidace na neškodné karboxylové kyseliny místo aldehydů, které by se mohly navazovat na apolipoprotein B. Paraoxonáza-1 v séru negativně ovlivňuje nové příhody u diabetu a aterosklerotického kardiovaskulárního onemocnění (ASKVO). Diabetes, dyslipidemie a zánět snižují aktivitu PON-1. Ablace lidského genu pro PON-1 nebo nadměrná exprese tohoto genu u zvířat posiluje nebo tlumí vnímavost k rozvoji aterosklerózy. Na rozdíl od apolipoproteinu AII zvyšují sérová koncentrace amyloidu A a myeloperoxidáza, apolipoprotein AI a poměr lecitin : cholesterol acyl transferáza antioxidační účinek PON-1. Strava a již užívané léky měnící hodnoty lipidů mohou účinnost PON snížit, je však třeba provádět specifickou léčbu zvyšující hodnoty PON-1.
Due to where paraoxonase-1 (PON-1)'s hydrophobic lipid domain is located, high-density lipoprotein (HDL) protects low-density lipoprotein (LDL) and the cell membranes on the outside from oxidation. It doesn't stop the formation of conjugated dienes, but it changes the products of lipid peroxidation into harmless carboxylic acids instead of aldehydes that could link to apolipoprotein B. Serum PON-1 inversely affects new events in diabetes and atherosclerotic cardiovascular disease (ASCVD). Diabetes, dyslipidemia, and inflammation decrease PON-1 activity. Human PON-1 gene ablation or overexpression in animals enhances or reduces atherosclerosis susceptibility. Unlike AII, serum amyloid A, and myeloperoxidase, apolipoprotein AI and lecithin : cholesterol acyl transferase boost PON-1 antioxidant activity. Diet and pre-existing lipid-modifying drugs may impact PON-1 activity, but specific PON-1-raising therapy is required.
- MeSH
- aryldialkylfosfatasa * fyziologie genetika krev škodlivé účinky MeSH
- ateroskleróza * genetika krev MeSH
- kardiovaskulární nemoci diagnóza terapie MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- lipoproteiny HDL fyziologie MeSH
- lipoproteiny MeSH
- peroxidace lipidů fyziologie MeSH
- polymorfismus genetický fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
This study summarizes the response of cyanobacterium Spirulina subsalsa HKAR-19 under simulated light conditions of photosynthetically active radiation (PAR), PAR+UV-A (PA), and PAR+UV-A+UV-B (PAB). Exposure to UV radiation caused a significant (P < 0.05) decrease in chlorophyll a, phycocyanin, and total protein. In contrast, total carotene content increased significantly (P < 0.05) under PA and PAB with increasing irradiation time. The photosynthetic efficiency of photosystem II also decreased significantly in PA and PAB radiation. We have also recorded a decrease in the fluorescence emission intensity of phycocyanin under PA and PAB exposure. The phycocyanin fluorescence shifted towards shorter wavelengths (blue-shift) after 72 h of PA and PAB exposure. Intracellular reactive oxygen species (ROS) levels increased significantly in PA and PAB. Fluorescence microscopic images showed an increase in green fluorescence, indicating ROS generation in UV radiation. We have also quantified ROS generation using green and red fluorescence ratio represented as G/R ratio. A 2-6-fold increase in antioxidative enzymes activity was observed to overcome the damaging effects caused by UV stress as compared to untreated control cultures. The lipid peroxidation was assessed in terms of malondialdehyde content which increases significantly (P < 0.05) as the duration of exposure increases. These results suggest that a combined effect of PAR, UV-A, and UV-B was more deleterious than an individual one.
- MeSH
- antioxidancia * metabolismus MeSH
- chlorofyl a metabolismus MeSH
- chlorofyl * metabolismus MeSH
- fotosyntéza * účinky záření MeSH
- fotosystém II (proteinový komplex) metabolismus MeSH
- fykocyanin * metabolismus MeSH
- karotenoidy metabolismus MeSH
- peroxidace lipidů účinky záření MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- Spirulina * účinky záření metabolismus MeSH
- ultrafialové záření * MeSH
- Publikační typ
- časopisecké články MeSH
Acetaldehyde can be found in human cells as a byproduct of various metabolic pathways, including oxidative processes such as lipid peroxidation. This secondary product of lipid peroxidation plays a role in various pathological processes, leading to various types of civilization diseases. In this study, the formation of free acetaldehyde induced by oxygen-centred radicals was studied in monocyte-like cell line U937. Exposure of U937 cells to peroxyl/alkoxyl radicals induced by azocompound resulted in the formation of free acetaldehyde. Acetaldehyde is formed by the cleavage of fatty acids, which represents the breakdown of fatty acids into smaller fragments initiated by the cyclization of lipid peroxyl radical and β-scission of lipid alkoxyl radical. The cleavage of fatty acids alters the integrity of the plasma and nuclear membrane, leading to the loss of cell viability. Understanding the pathological processes of acetaldehyde formation is an active area of research with potential implications for preventing and treating various diseases associated with oxidative stress.
- MeSH
- acetaldehyd * MeSH
- lidé MeSH
- mastné kyseliny metabolismus MeSH
- monocyty * metabolismus MeSH
- peroxidace lipidů MeSH
- reaktivní formy kyslíku MeSH
- U937 buňky MeSH
- volné radikály metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Recent research has highlighted the pivotal role of lipoxygenases in modulating ferroptosis and immune responses by catalyzing the generation of lipid peroxides. However, the limitations associated with protein enzymes, such as poor stability, low bioavailability, and high production costs, have motivated researchers to explore biomimetic materials with lipoxygenase-like activity. Here, we report the discovery of lipoxygenase-like two-dimensional (2D) MoS2nanosheets capable of catalyzing lipid peroxidation and inducing ferroptosis. The resulting catalytic products were successfully identified using mass spectrometry and a luminescent substrate. Unlike native lipoxygenases, MoS2 nanosheets exhibited exceptional catalytic activity at extreme pH, high temperature, high ionic strength, and organic solvent conditions. Structure-activity relationship analysis indicates that sulfur atomic vacancy sites on MoS2 nanosheets are responsible for their catalytic activity. Furthermore, the lipoxygenase-like activity of MoS2 nanosheets was demonstrated within mammalian cells and animal tissues, inducing distinctive ferroptotic cell death. In summary, this research introduces an alternative to lipoxygenase to regulate lipid peroxidation in cells, offering a promising avenue for ferroptosis induction.
- MeSH
- biomimetické materiály chemie farmakologie metabolismus MeSH
- disulfidy * chemie metabolismus MeSH
- ferroptóza * účinky léků MeSH
- katalýza MeSH
- lidé MeSH
- lipoxygenasa * metabolismus chemie MeSH
- molybden chemie metabolismus MeSH
- myši MeSH
- nanostruktury chemie MeSH
- peroxidace lipidů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: Radiotherapy (RT) is an integral treatment part for patients with head and neck squamous cell carcinoma (HNSCC), but radioresistance remains a major issue. Here, we use MitoTam, a mitochondrially targeted analogue of tamoxifen, which we aim to stimulate ferroptotic cell death with, and sensitize radioresistant cells to RT. MATERIALS AND METHODS: We assessed viability, reactive oxygen species (ROS) production, disruption of mitochondrial membrane potential, and lipid peroxidation in radiosensitive (UT-SCC-40) and radioresistant (UT-SCC-5) HNSCC cells following MitoTam treatment. To assess ferroptosis specificity, we used the ferroptosis inhibitor ferrostatin-1 (fer-1). Also, total antioxidant capacity and sensitivity to tert-butyl hydroperoxide were evaluated to assess ROS-responses. 53BP1 staining was used to assess radiosensitivity after MitoTam treatment. RESULTS: Our data revealed increased ROS, cell death, disruption of mitochondrial membrane potential, and lipid peroxidation following MitoTam treatment in both cell lines. Adverse effects of MitoTam on cell death, membrane potential and lipid peroxidation were prevented by fer-1, indicating induction of ferroptosis. Radioresistant HNSCC cells were less sensitive to the effects of MitoTam due to intrinsic higher antioxidant capacity. MitoTam treatment prior to RT led to superadditive residual DNA damage expressed by 53BP1 foci compared to RT or MitoTam alone. CONCLUSION: MitoTam induced ferroptosis in HNSCC cells, which could be used to overcome the elevated antioxidant capacity of radioresistant cells and sensitize such cells to RT. Treatment with MitoTam followed by RT could therefore present a promising effective therapy of radioresistant cancers. STATEMENT OF SIGNIFICANCE: Radiotherapy is applied in the treatment of a majority of cancer patients. Radioresistance due to elevated antioxidant levels can be overcome by promoting ferroptotic cell death combining ROS-inducing drug MitoTam with radiotherapy.
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku radioterapie farmakoterapie patologie MeSH
- ferroptóza * účinky léků MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- nádorové buněčné linie MeSH
- nádory hlavy a krku * radioterapie patologie farmakoterapie MeSH
- peroxidace lipidů * účinky léků MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- spinocelulární karcinom radioterapie patologie farmakoterapie MeSH
- tamoxifen farmakologie MeSH
- tolerance záření * účinky léků MeSH
- viabilita buněk účinky léků účinky záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Koletsky rats, the genetically obese strain of spontaneously hypertensive rats (SHROB), are the well-accepted animal model of human metabolic syndrome. They are characterized by early onset obesity, spontaneous hypertension, hyperinsulinemia, hyperlipidemia, proteinuria and shortened life-span. One of the factors in the pathogenesis of metabolic syndrome is oxidative stress. The aim of the present study was to compare two parameters related to oxidative stress: the levels of the main intracellular antioxidant, reduced glutathione as well as the indirect indicator of lipid peroxidation damage, thiobarbituric acid-reactive substances (TBARS) in heart, renal cortex and medulla and liver in male lean spontaneously hypertensive rats (SHR) and obese Koletsky rats. We did not find any significant differences in these markers in heart and kidneys. However, we found significantly lower glutathione level in Koletsky rat liver compared with SHR (5.03+/-0.23 vs. 5.83+/-0.14 μmol/g tissue, respectively). On the contrary, we observed significantly higher TBARS levels in Koletsky rat liver compared with SHR (28.56+/-2.15 vs. 21.83+/-1.60 nmol/mg protein, respectively). We conclude that the liver is the most sensitive tissue to oxidative damage with the significantly decreased concentration of glutathione and the significantly increased concentration of TBARS in obese Koletsky rats in comparison with lean control SHR.
- MeSH
- glutathion * metabolismus MeSH
- hypertenze metabolismus MeSH
- játra * metabolismus MeSH
- krysa rodu rattus MeSH
- látky reagující s kyselinou thiobarbiturovou metabolismus MeSH
- ledviny metabolismus MeSH
- myokard metabolismus MeSH
- obezita * metabolismus MeSH
- oxidační stres * fyziologie MeSH
- peroxidace lipidů * MeSH
- potkani inbrední SHR * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Oxidative stress status, as a disruption of redox homeostasis, in the blood sera of Wistar rats caused by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Throughout this study, each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Then, seven days after the last oximes' application, markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, reduced glutathione, GSH, and oxidized glutathione, GSSG), were determined. Oxidative stress parameters, MDA and AOPP were significantly highest in the K048-, K074- and K075-treated groups (p < 0.001). The activity of CAT was significantly elevated in the obidoxime-treated group (p < 0.05), while treatment with K027, K048, and K074 induced high elevation in SOD levels (p < 0.01, p < 0.001). Interestingly, the activity of GSH in each oxime-treated group was significantly elevated. Unlike, treatment with obidoxime caused elevation in GSSG levels (p < 0.01). As a continuation of our previously published data, these results assure that applied oximes following subacute treatment ameliorated the oxidative status and further adverse systemic toxic effects in rats.
- MeSH
- antioxidancia metabolismus farmakologie MeSH
- biologické markery * krev MeSH
- glutathion * krev metabolismus MeSH
- katalasa metabolismus krev MeSH
- krysa rodu rattus MeSH
- malondialdehyd krev metabolismus MeSH
- oxidační stres * účinky léků MeSH
- oximy * farmakologie MeSH
- peroxidace lipidů účinky léků MeSH
- potkani Wistar * MeSH
- produkty pokročilé oxidace proteinů krev MeSH
- reaktivátory cholinesterasy farmakologie MeSH
- superoxiddismutasa metabolismus krev MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
A tumour suppressor miRNA, miR-128-3p, is widely involved in various biological processes and has been found to get downregulated in breast cancer patients. We previously published that ectopically expressed miR-128-3p suppressed migration, invasion, cell cycle arrest, and breast cancer stem cells. In the present study, we explored the role of Empagliflozin (EMPA) as a miR-128-3p functionality-mimicking drug in inducing ferroptosis by inhibiting CD98hc. Given that CD98hc is one of the proteins critical in triggering ferroptosis, we confirmed that miR-128-3p and EMPA inhibited SP1, leading to inhibition of CD98hc expression. Further, transfection with siCD98hc, miR-128-3p mimics, and inhibitors was performed to assess their involvement in the ferroptosis of anoikis-resistant cells. We proved that anoikis-resistant cells possess high ROS and iron levels. Further, miR-128-3p and EMPA treatments induced ferroptosis by inhibiting GSH and enzymatic activity of GPX4 and also induced lipid peroxidation. Moreover, EMPA suppressed bioluminescence of 4T1-Red-FLuc induced thoracic cavity, peritoneal tumour burden and lung nodules in an in-vivo metastatic model of breast cancer. Collectively, we revealed that EMPA sensitized the ECM detached cells to ferroptosis by synergically activating miR-128-3p and lowering the levels of SP1 and CD98hc, making it a potential adjunct drug for breast cancer chemotherapy.
- MeSH
- anoikis * účinky léků genetika MeSH
- benzhydrylové sloučeniny * farmakologie MeSH
- ferroptóza * účinky léků genetika MeSH
- glifloziny farmakologie MeSH
- glukosidy * farmakologie MeSH
- kotransportní proteiny pro sodík a fosfát - typ IIb MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prsu * patologie metabolismus farmakoterapie genetika MeSH
- peroxidace lipidů účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- regulace genové exprese u nádorů * účinky léků MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The study was designed to evaluate the medical relevance of total homocysteine (tHcy), total antioxidant capacity (TAC), and malondialdehyde (MDA) before and after chemotherapy for women with breast cancer (BRCA). Blood samples were taken from Oncology Unit in Merjian Teaching hospital in Hilla city (Iraq). Sixty patients suffering from breast cancer (BRCA) were enrolled in this study, and twenty-one apparently healthy subjects were considered as a control group control. We found that significantly increased lipid peroxidation, measured as MDA, was demonstrated in the serum of BRCA patients who were not taken any medication was higher than in the control group (P<0.01) were (25±15) nmol/ml of MDA levels in BRCA patient and (14.5±7.9) nmol/ml of MDA levels in healthy controls. We found that treatment by chemotherapy resulted in a significant increase in MDA levels when compared with MDA levels in patients who were not taken any medication. The tHcy level in BRCA patients before and after treatment were changed. In addition, it is found that the mean serum TAC levels in BRCA patients were significantly less than in the control group. Moreover, a positive correlation was observed between the activity of chemotherapy and MDA levels in the patient and the same correlation between tHcy levels and TAC levels while a negative correlation was observed between TAC levels with MDA levels in the patient group.
The species of Comamonas testosteroni is the most common human pathogen of the genus, which can be associated with acute appendicitis, infections of the bloodstream, the peritoneal cavity, cerebrospinal fluid, inflammatory bowel disease, and in general, bacteremia. According to the literature, Comamonas testosteroni has destructive activity to a wide range of toxic chemical compounds, including chlorobenzenes. The specified strains were isolated from the soil of the organochlorine waste landfill, where hexachlorobenzene (HCB) was predominant. These strains were expected to be capable of degrading HCB. Microbiological (bacterial enrichment and cultivating, bacterial biomass obtaining), molecular biology, biochemical (enzymatic activities, malondialdehyde measuring, peroxidation lipid products measuring), and statistical methods were carried out in this research. The reaction of both strains (UCM B-400 and UCM B-401) to the hexachlorobenzene presence differed in the content of diene and triene conjugates and malondialdehyde, as well as different catalase and peroxidase activity levels. In terms of primary peroxidation products, diene conjugates were lower, except conditions with 20 mg/L HCB, where these were higher up to two times, than the pure control. Malondialdehyde in strain B-400 cells decreased up to five times, in B-401, but increased up to two times, compared to the pure control. Schiff bases in strain B-400 cells were 2-3 times lower than the pure control. However, in B-401 cells Schiff bases under higher HCB dose were in the same level with the pure control. Catalase activity was 1.5 times higher in all experimental variants, compared to the pure control (in the strain B-401 cells), but in the B-400 strain, cells were 2 times lower, compared to the pure control. The response of the two strains to hexachlorobenzene was similar only in peroxidase activity terms, which was slightly higher compared to the pure control. The physiological response of Comamonas testosteroni strains to hexachlorobenzene has a typical strain reaction. The physiological response level of these strains to hexachlorobenzene confirms its tolerance, and indirectly, the ability to destroy the specified toxic compound.
- MeSH
- antioxidancia MeSH
- chlorbenzeny MeSH
- Comamonas testosteroni * MeSH
- hexachlorbenzen * MeSH
- katalasa MeSH
- lidé MeSH
- lipidy MeSH
- malondialdehyd MeSH
- peroxidace lipidů MeSH
- půda MeSH
- Schiffovy báze MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
