Browsing by Subject "Reactive oxygen species"

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    An immunohistochemical study of NFE2L2, KEAP1 and 8-hydroxy-2'-deoxyguanosine and the EMT markers SNAI2, ZEB1 and TWIST1 in metastatic melanoma
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Hintsala, Hanna Riikka; Haapasaari, Kirsi Maria; Soini, Ylermi; Karihtala, Peeter
    Background: Little is known regarding the role of redox balance regulators in metastatic melanomas, but there is some evidence for a link between epithelial-to-mesenchymal transition (EMT) and cellular redox status. Methods: We compared the immunohistochemical expression of nuclear factor erythroid-2-related factor 2 (NFE2L2), Kelch-like ECH-associated protein 1 (KEAP1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), TWIST1, SNAI2 and ZEB1 between primary melanomas and metastases in a cohort of 23 nevi, 66 malignant melanomas and 22 metastases. Results: Nuclear NFE2L2 expression was higher (p=0.003) and cytoplasmic KEAP1 lower (p=0.026) in metastatic lesions than at primary sites. Nuclear NFE2L2 expression was associated with the presence of distant metastases (p=0.040) and with nuclear TWIST1 expression (p=0.002). Patients having both NFE2L2 and TWIST1 expression in nuclei had an extremely poor prognosis (p=0.0003). In multivariate analysis nuclear TWIST1 expression was an independent predictor of a poorer prognosis (HR 2.99, 95% CI 1.17-7.69; p=0.023) and the invasive TWIST1/ZEB1 phenotype showed poorer melanoma-specific survival (HR 7.28, 95% CI 2.23-23.77; p=0.001). Nuclear expression of 8-OHdG (p=0.001) was lower at metastatic sites than in primary lesions. Conclusions: EMT signalling and the KEAP1/NFE2L2- axis are likely to be involved in metastatic spread of malignant melanoma and also appear to have potential interactions.
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    Anti-death strategies against oxidative stress in grafted mesenchymal stem cells
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Woochul, Chang; Byeong-Wook, Song; Jae-Youn, Moon; Min-Ji, Cha; Onju, Ham; Se-Yeon, Lee; Eunmi, Choi; EunHyum, Choi; Ki-Chul, Hwang
    Mesenchymal stem cells (MSCs) possess the potential for use in cell-based therapy for repair of myocardial injury. The therapeutic potential of MSCs is based on the capacity of MSCs to differentiate into cardiac tissue and release paracrine factors. However, a major problem in the clinical application of MSC-based therapy is the poor viability of transplanted MSCs at the site of graft due to harsh microenvironment conditions, such as ischemia and/or anoikis. Ischemia after myocardial infarction (MI) and interaction of MSCs with their niche is associated with increased production of reactive oxygen species (ROS). ROS hinder cell adhesion and induce detachment of cells, which induces anoikis signals in implanted MSCs. Therefore, strategies to regulate oxidative stress following the implantation of MSCs are therapeutically attractive. In this review, we first describe ROS as a major obstacle in MSC-based therapy and focus on manipulation of implanted MSCs to reduce ROS-mediated anoikis.
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    Antioxidant enzyme levels in cancer
    (Murcia : F. Hernández, 1997) Oberley, T.D.; Oberley, L.W.
    Normal cells are protected by antioxidant enzymes from the toxic effects of high concentrations of reactive oxygen species generated during cellular metabolism. Even though cancer cells generate reactive oxygen species, it has been demonstrated biochemically that antioxidant enzyme levels are low in most animal and human cancers. However, a few cancer types have been found to have elevated levels of antioxidant enzymes, particularly manganese superoxide dismutase. Morphologic studies of animal and human cancer have confirmed that although the majority of tumor cell types from severa1 organ systems have low antioxidant enzymes, adenocarcinomas may have elevated manganese superoxide dismutase and catalase levels. However, al1 cancers examined to date have some imbalance in antioxidant enzyme levels compared with the cell of origin. Antioxidant enzyme importance in cancer genesis has been difficult to evaluate in early cancerous lesions using biochemical techniques because such lesions are small and therefore below the leve1 of detection. Using immunohistochemical techniques, early lesions of human and animal cancers were demonstrated to have low antioxidant enzymes, thus suggesting a role for these enzymes both in the genesis of cancer and the malignant phenotype. Al1 but one human cancer cell type (the granular cell variant of human renal adenocarcinoma) examined showed both low catalase and glutathione peroxidase levels, suggesting that most cancer cell types cannot detoxify hydrogen peroxide. Our results to date are used to propose new cancer therapies based on modulation of cellular redox state.
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    Broccoli byproduct extracts attenuate the expression of UVB-induced proinflammatory cytokines in HaCaT keratinocytes
    (MDPI, 2024-12-02) Borja Martínez, María; Pedreño García, María Ángeles; Sabater Jara, Ana Belén; Biología Vegetal
    Broccoli byproducts are an important source of bioactive compounds, which provide important benefits for human skin due mainly to their antioxidant and anti-inflammatory properties. The primary target of UVB radiation is the basal layer of cells in the epidermis, with keratinocytes being the most abundant cell population in this layer. Given the wide range of side effects caused by exposure to UVB radiation, reducing the amount of UV light that penetrates the skin and strengthening the protective mechanisms of the skin are interesting strategies for the prevention of skin disorders. This work aims to evaluate the protective mechanisms triggered by broccoli by-products extract (BBE) on HaCaT keratinocytes exposed to UVB radiation as well as the study of the regenerative effect of these extracts on the barrier of skin keratinocytes damaged by superficial wounds as a strategy to revalorize this agricultural waste. The results obtained revealed that the BBEs exhibited a high cytoprotective effect on the HaCaT exposed to UVB light, allowing it to effectively reduce the intracellular content of ROS, as well as effectively attenuating the increase in proinflammatory cytokines (IL-1β, IL-6, IL-78, TNF-α) and COX-2 induced by this type of radiation. Furthermore, the BBE could be an excellent regenerative agent for skin wound repair, accelerating the migration capacity of keratinocytes thus contributing to the valorization of this byproduct as a valuable ingredient in cosmetic formulations.
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    Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes
    (2016) Asensio Lopez, Maria del Carmen; Sanchez Mas, Jesus; Pascual Figal, Domingo A.; Fernandez Belda, Francisco; Lax Pérez, Antonio Manuel; Soler Pardo, Fernando; Medicina
    In atrial-derived HL-1 cells, ryanodine receptor and Naþ/Ca2þ-exchanger were altered early by 5 mM doxorubicin. The observed effects were an increase of cytosolic Ca2þ at rest, ensuing ryanodine receptor phosphorylation, and the slowing of Ca2þ transient decay after caffeine addition. Doxorubicin triggered a linear rise of reactive oxygen species (ROS) with no early effect on mitochondrial inner membrane potential. Doxorubicin and ROS were both detected in mitochondria by colocalization with fluorescence probes and doxorubicin-induced ROS was totally blocked by mitoTEMPO. The NADPH oxidase activity in the mitochondrial fraction was sensitive to inhibition by GKT137831, and doxorubicin-induced ROS decreased gradually as the GKT137831 concentration added in preincubation was increased. When doxorubicin-induced ROS was prevented by GKT137831, the kinetic response revealed a permanent degree of protection that was consistent with mitochondrial NADPH oxidase inhibition. In contrast, the ROS induction by doxorubicin after melatonin preincubation was totally eliminated at first but the effect was completely reversed with time. Limiting the source of ROS production is a better alternative for dealing with oxidative damage than using ROS scavengers. The short-term effect of doxorubicin on Ca2þ transporters involved in myocardiac contractility was dependent on oxidative damage, and so the impairment was subsequent to ROS production.
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    How bad is brazilian ginseng extract for reproductive parameters in mice?
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Dias, F.C.R.; Machado Neves, M.; Lima, G.D.A.; Martins, A.L.P.; Menezes, T.P.; Melo, F.C.S.A.; Gomes, M.L.M.; Cupertino, M.C.; Otoni, W.C.; Matta, S.L.P.
    Properties attributed to the Panax ginseng are also attributed to the Brazilian ginseng, such as adaptogenic and aphrodisiac effects. There are studies demonstrating that the Brazilian ginseng (BGE) possibly increases the serum levels of testosterone and nitric oxide in mice and rats. The present study aimed to evaluate the effects of its extract on male fertility and sperm quality. Male Swiss mice (n=60) were divided into six groups. The control animals were provided 0.5 mL of water, and 0.5 mL of water containing 7 mg/kg per day (d) sildenafil citrate. Other animals were treated with BGE at 100 mg/kg/d, 200 mg/kg/d, and 400 mg/kg/d by gavage for 42 days. Finally, animals from the last group received 200 mg/kg BGE every 3 days (3- 3d) by gavage for 42 days. The results showed a reduction in the number of resistant spermatids in the testis and damage to daily sperm production, culminating in a reduction in the number of epididymal spermatozoa. Although the sperm quality decreased in all experimental animals, only males treated with BGE 100 mg/kg/d showed pre and post implantation embryo losses. We concluded that BGE alters sperm viability compromising the embryonic development after implantation
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    Impact of Seminal Plasma Antioxidants on Donkey Sperm Cryotolerance
    (MDPI, 2022-02-18) Catalán, Jaime; Yáñez Ortiz, Iván; Tvarijonaviciute, Asta; González Arostegui, Luis Guillermo; Peres Rubio, Camila; Yeste, Marc; Miró, Jordi; Barranco Cascales, Isabel; Medicina y Cirugía Animal
    This study investigated whether the activities of the antioxidant components of donkey seminal plasma (SP)-both enzymatic (superoxide dismutase (SOD), catalase-like (CAT), glutathione peroxidase-like (GPX), and paraoxonase type 1 (PON1)) and non-enzymatic (measured in terms of total thiol, copper-reducing antioxidant capacity (CUPRAC), ferric-reducing ability of plasma (FRAP), and Trolox equivalent antioxidant capacity (TEAC))-and oxidative stress index (OSI) are related to sperm cryotolerance. For this purpose, 15 ejaculates from jackasses (one per individual) were collected and split into two aliquots. The first one was used for measuring the activities levels of enzymatic and non-enzymatic antioxidants and OSI in SP, whereas the other aliquot was cryopreserved. Before cryopreservation, sperm quality parameters (concentration, motility, and viability) were evaluated. After thawing, sperm motility, plasma membrane integrity, lipid disorder, mitochondrial membrane potential, reactive oxygen species (ROS), and calcium intracellular levels were also determined. Based on the percentages of total motility (TM) and of sperm with an intact plasma membrane (SYBR14+/PI-) after thawing, samples were classified as good-freezability (GFE) or poor-freezability (PFE) ejaculates through cluster analyses. The SP activity levels of enzymatic (SOD and PON1) and non-enzymatic antioxidants (CUPRAC, FRAP, and TEAC) were higher (p < 0.05) in GFE than in PFE, whereas SP-OSI was higher (p < 0.05) in PFE than in GFE. In addition, the activity levels of SOD, PON1, GPX, CUPRAC, FRAP, and TEAC were positively (p < 0.05) related to post-thaw sperm motility and plasma membrane integrity and negatively to intracellular ROS levels. The SP-OSI was negatively correlated (p < 0.05) to post-thaw sperm quality parameters and positively to intracellular ROS levels. It can thus be concluded that donkey SP antioxidants are related to sperm cryotolerance and that measurements of antioxidants PON1, SOD, CUPRAC, FRAP, and TEAC, as well as SP-OSI, could be used as markers of sperm cryotolerance. Further research addressing the relationship of these antioxidants and SP-OSI with sperm cryotolerance and their potential use as freezing markers is warranted.
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    Seminal plasma antioxidants are related to sperm cryotolerance in the horse
    (MDPI, 2022-06-28) Catalán, Jaime; Yánez Ortiz, Iván; Tvarijonaviciute, Asta; González Aróstegui, Luis Guillermo; Peres Rubio, Camila; Barranco Cascales, Isabel; Yeste, Marc; Miró, Jordi; Medicina y Cirugía Animal
    The objective of this study was to determine the relationship of enzymatic (superoxide dismutase, SOD; glutathione peroxidase, GPX; catalase, CAT; and paraoxonase type 1, PON1) and non-enzymatic antioxidants (measured in terms of: Trolox equivalent antioxidant capacity, TEAC; cupric-reducing antioxidant capacity, CUPRAC; and ferric-reducing ability of plasma, FRAP), as well as the oxidative stress index (OSI) in seminal plasma (SP) with the resilience of horse sperm to freeze-thawing. Twenty-one ejaculates (one per individual) were collected and split into two aliquots: the first was used to harvest the SP and assess the activity levels of antioxidants and the OSI, and the second one was cryopreserved. The following post-thaw sperm quality parameters were evaluated: sperm motility, plasma membrane and acrosome integrity, mitochondrial membrane potential, intracellular levels of reactive oxygen species (ROS), and plasma membrane lipid disorder. Based on post-thaw total motility (TM) and plasma membrane integrity (SYBR14+/PI−), ejaculates were hierarchically (p < 0.001) clustered into two groups of good (GFE) and poor (PFE) freezability. The SP activity levels of PON1, SOD, and TEAC were higher (p < 0.05) in GFE than in PFE, showing a positive relationship (p < 0.05) with some sperm motility parameters and with plasma membrane (PON1 and TEAC) and acrosome (SOD and TEAC) integrity. In contrast, OSI was higher (p < 0.05) in the SP of PFE than in that of GFE, and was negatively correlated (p < 0.05) to some sperm motility parameters and to plasma membrane and acrosome integrity, and positively (p < 0.05) to the percentage of viable sperm with high plasma membrane lipid disorder. In conclusion, enzymatic (PON1 and SOD) and non-enzymatic (TEAC) antioxidants of SP are related to horse sperm cryotolerance. In addition, our results suggest that PON1 could be one of the main antioxidant enzymes involved in the control of ROS in this species. Further investigation is needed to confirm the potential use of these SP-antioxidants and OSI to predict sperm cryotolerance in horses.
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    Serum biomarkers of oxidative stress in dogs with idiopathic inflammatory bowel disease
    (Elsevier, 2017-03) Peres Rubio, Camila; Martínez-Subiela, S.; Tvarijonaviciute, Asta; Cerón, J.J.; Allenspach, K.; Hernández Ruiz, Josefa; Medicina y Cirugía Animal
    The objective of this work was to study and compare a panel of various serum biomarkers evaluating both the antioxidant response and oxidative damage in dogs with idiopathic inflammatory bowel disease (IBD). Eighteen dogs with IBD and 20 healthy dogs were enrolled in the study. Trolox equivalent antioxidant capacity (TEAC), cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of the plasma (FRAP), total thiol concentrations, and paraoxonase 1 (PON1) activity were evaluated in serum to determine antioxidant response. To evaluate oxidative status, ferrous oxidation-xylenol orange (FOX), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species production (ROS) concentrations in serum were determined. Mean concentrations of all antioxidant biomarkers analyzed, with exception of FRAP, were significantly lower (P < 0.0001) in the sera of dogs with IBD than in healthy dogs. The oxidant markers studied were significantly higher (P < 0.0001) in sera of dogs with IBD than in healthy dogs. These findings support the hypothesis that oxidative stress could play an important role in the pathogenesis of canine IBD.
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    The pivotal role of PDGF and its receptor isoforms in adipose-derived stem cells
    (Universidad de Murcia. Servicio de publicaciones, 2015) Kim, Won-Serk; Park, Hyoung-Sook; Sung, Jong-Hyuk
    Platelet-derived growth factor (PDGF) is one of the growth factors that reportedly regulates cell growth and division of mesenchymal cells. Although PDGF isoforms and their receptors reportedly play a pivotal role in mesenchymal stem cell regulation, there is a paucity of literature reviewing the role of PDGF in adipose-derived stem cells (ASCs). Therefore, we summarized previous reports on the expression and functional roles of PDGF and its receptor isoforms in this review. In addition, we examined findings pertaining to underlying molecular mechanisms and signaling pathways with special focus on PDGF-D/PDGFRβ. ASCs only express PDGF-A, -C, -D, PDGFRα, and PDGFRβ. PDGFRα expression decreases with adipocyte lineage, while PDGFRβ inhibits white adipocyte differentiation. In addition, PDGFRβ induces proliferation, migration, and angiogenesis and upregulates the expression of paracrine factors in ASCs. Although PDGF-B and -D mediate their functions mainly by PDGFRβ and ROS generation, there are many differences between them in terms of regulating ASCs. PDGF-D is endogenous, generates ROS via the mitochondrial electron transport system, and regulates the autocrine loop of ASCs in vivo. Furthermore, PDGFD has stronger mitogenic effects than PDGF-B.