DigitalUM :: Browsing by Subject "Oxidative stress"

Browsing by Subject "Oxidative stress"

Now showing 1 - 20 of 55

Open Access
8-weeks training program attenuates mitochondrial oxidative stress in the liver of emotionally stressed rats
(Murcia : F. Hernández, 2006) Rosety-Rodriguez, M.; Ordóñez Muñoz, F.J.; Rosety, I.; Frias, L.; Rosety, M.A.; Rosety, J.M.; Rosety, M.A.
In recent years it has been shown that emotional stress induced by immobilization may change the balance between pro-oxidant and antioxidant factors inducing oxidative damage. On the other hand, contradictory views exist concerning the role of physical activity on redox metabolism. Consequently, the present work was designed to assess the influence of an 8-week moderate swimming training program in emotionally stressed rats. Sixty 1-month-old male albino Wistar rats weighing 125-135 g were used in this experimental study. They were divided into three groups, as Control (lot A; n=20), Stressed (lot B; n=20) and Stressed & Exercised (lot C; n=20). Rats were stressed by placing the animals in a 25 x 7 cm plastic bottle 1 h/day, 5 days a week for 8 weeks. Protein carbonyl content values in liver homogenates were significantly increased in stressed animals (0.58±0.02 vs 0.86±0.03; p=0.018) which clearly indicated that emotional stress was associated with oxidative stress. Ultrastructural alterations, predominantly mitochondrial swelling and the decrease of cristae number observed by electron microscopy represented direct evidence of membrane injury. The most striking feature of our study was that we also found differences between stressed rats and stressed rats that performed our 8 week training program. Consequently our results highlight the potential benefit of a moderate training program to reduce oxidative damage induced by emotional stress since it attenuated protein oxidation and mitochondrial alterations.
Open Access
Acute cardiotoxicity induced by doxorubicin in right ventricle is associated with increase of oxidative stress and apoptosis in rats
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Anghel, N.; Herman, H.; Balta, C.; Rosu, M.; Stan, M.S.; Nita, D.; Ivan, A.; Galajda, Z.; Ardelean, A.; Dinischiotu, A.; Hermenean, A.
Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but its efficiency is seriously limited by the risk of developing cardiomyopathy. The most recognized cardiotoxic effect is left ventricular (LF) dysfunction, but MRI and echocardiography data demonstrated significant right ventricle (RV) function impairment. In order to clarify this aspect, the present study investigated the potential of DOX to induce acute RV cardiotoxicity at the same time as LV impairment. Rats were intraperitoneally (i.p.) injected with a single dose of 15 mg/kg DOX. DOXtreated rats were characterized by decreased body and heart weights, elevated levels of creatine kinase (CKMB) and lactate dehydrogenase (LDH) activities compared to controls. Biochemical analyses on RV tissue revealed that the level of malondialdehyde (MDA) was significant increased (p<0.05) and activities of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPX) antioxidant enzymes were decreased by 13%, 27% and 18%, respectively, compared to control. Histopathogical and electron microscopic studies revealed DOX-induced damage in both ventricles and an increase of interstitial collagen fibers compared to controls (p<0.001), whereas immunohistochemical analysis showed weak and irregular desmin expression. Furthermore, mitochondrion-induced apoptotic pathways were also activated in both ventricles, as reflected by the up-regulation of Bax/Bcl-2 mRNA expression ratio (p<0.001) and increase of Bax and caspase-3 protein expression, as well as by the significant elevation of TUNEL positive nuclei, compared to controls (p<0.001). The results showed that DOX exerted RV toxic effects at the same time as those reported in the LV, which might be mediated through the mitochondrial-dependent apoptosis.
Open Access
Alleviative effect of myricetin on ochratoxin A-induced oxidative stress in rat renal cortex: histological and biochemical study
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Abd El-haleem, Manal R.; Kattaia, Asmaa A.A.; Abd El-Baset, Samia A.; El Sayed Mostafa, Heba
Ochratoxins (OTA) are secondary metabolites of Aspergillus and Penicillium. The detoxification of OTA has been of major interest due to its widespread threat to human health. We aimed to investigate the possible alleviative effect of myricetin (MYR) against OTA-induced damage in renal cortex of rats. Thirty adult male albino rats were randomized into five equal groups: control (untreated), vehicle control (0.5 ml corn oil/day including dimethylsulfoxide [DMSO]), MYR (100 mg MYR/kg b.w./day in distilled water), OTA (0.5 mg OTA/kg b.w./day; dissolved in 10% DMSO and then corn oil) and OTA + MYR group (received OTA and MYR at similar doses). All treatments were given by oral gavage for 2 weeks. At the end of the experiment, renal cortices were processed for light and electron microscope examinations. Immunohistochemical staining for localization of proliferating cell nuclear antigen (PCNA), p53 and transforming growth factor beta 1 (TGF-β1) was carried out. Biochemical analysis of tissue glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress. OTA administration induced deleterious renal injury evidenced by the structural and ultra-structural changes. Immunohistochemical expression of p53, PCNA and TGF-β1 were significantly up regulated compared with control. Alterations in antioxidant parameters supported that oxidative stress was one of the mechanisms involved in OTA toxicity. On the contrary, co-administration of MRY partially ameliorated OTAinduced renal injury. We suggest the potential effectiveness of MYR to counteract OTA-induced toxic oxidative stress on the renal cortex.
Open Access
Ameliorative effects of HGF-overexpressed exosomes derived from ADMSCs on oxidative stress in hepatic fibrosis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhou, Hanyu; Wu, Yanyan; Xue, Junchao; Yu, Liushenyan
Background. Hepatic fibrosis, ultimately causing hepatic sclerosis, remains significant health concerns. Adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes (Exo) exhibit amelioration of liver injury. Hepatocyte growth factor (HGF) regulates hepatocyte growthn. However, its involvement during hepatic fibrosis remains unclear. Methods. Isolation of ADMSCs and Exo, transfection of HGF overexpression, and activation of hepatic stellate cells (HSCs) by Angiotensin II (AngII) were conducted. Cells were randomized into HSC, AngII-HSC, ADMSCs-Exo, ADMSCsblank-Exo, and ADMSCsHGF-Exo, DPI, LY294002, and SB203580 groups. MTT for cell viability, cell migration, and flow cytometry for ROS were performed. BALB/c mice were treated with CCL4 for hepatic fibrosis models. The mice were randomized into Control, PBS, ADMSCs-Exo, ADMSCsblank-Exo, and ADMSCsHGF-Exo groups (n=6). HE, Sirius red, and Oil Red O staining, liver function indicators, and ELISA for oxidative stress were performed. ROS generation-related and PI3K/Akt/ P38MAPK-related factors were detected by immunofluorescence, immunohistochemistry, and western blot. Results. After identification of ADMSC-Exo and transfection, AngII increased cell viability, migration, Collagen I (CoLI), α-smooth muscle actin (α-SMA), ROS, NADPH oxidase 4 (NOX4), PI3K, p-Akt, p-P38MAPK, ras-related C3 botulinum toxin substrate 1 (RAC1), p47phox, and p22phox expression. However, ADMSCsHGF-Exo, DPI, LY294002, and SB203580 reversed the above effects. Moreover, ADMSCsHGF-Exo inhibited pathological damage, fibrosis, lipid accumulation, ALT, AST, TBIL, CoLI, α-SMA, NOX4, MDA, PI3K, P-Akt, and P-P38MAPK expression, and increased ALB, SOD, GPx, CAT, GSH, Mn-SOD, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase levels in hepatic fibrosis mice. Conclusion. ADMSCsHGF-Exo attenuated hepatic fibrosis by inhibiting oxidative stress through activating the PI3K/Akt/P38MAPK pathway, providing valuable insights for potential treatment of liver fibrosis.
Open Access
Asiatic acid improves high-fat-diet-induced osteoporosis in mice via regulating SIRT1/FOXO1 signaling and inhibiting oxidative stress
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Chen, Xiaosi; Han, Dengpeng; Liu, Tianfeng; Huang, Chengshuo; Hu, Zibing; Tan, Xiaoyan; Wu, Shaoke
Asiatic acid can attenuate osteoporosis through suppressing adipogenic differentiation and osteoclastic differentiation. Oxidative stress enhances osteoclastic differentiation but represses osteogenic differentiation to promote osteoporosis. However, the role and mechanism of asiatic acid in osteoporosis have not been reported. Firstly, mice were fed with high-fatdiet (HFD) with or without asiatic acid for 16 weeks. Data from an automatic biochemical analyzer showed that HFD induced down-regulation of high-density lipoprotein (HDL) and an increase of serum levels of triglyceride (TG), total cholesterol (TC) and low-density lipoprotein (LDL). However, asiatic acid administration attenuated the decrease of HDL and increase of serum TG, TC and LDL in osteoporotic mice. Secondly, HFD induced high levels of malondialdehyde (MDA) and reactive oxygen species (ROS), low levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in osteoporotic mice. However, the levels of MDA, ROS, SOD and GSH-Px in osteoporotic mice were reversed by asiatic acid administration. (this section is unclear and requires revision) Asiatic acid administration reduced expression of c-telopeptide of type 1 collagen (CTX-1), enhanced alkaline phosphatase (ALP) and procollagen type 1 N-terminal propeptide (P1NP) in HFD-induced osteoporotic mice. (this section is unclear and requires revision) Thirdly, asiatic acid promoted calcium deposition in bone marrow cells and osteogenic differentiation in osteoporotic mice, but decreased ALP in bone marrow cells. Lastly, asiatic acid enhanced SIRT1 and nuclear FOXO1 (Nu-FOXO1) expression, while it reduced Acetyl FOXO1 (AcFOXO1) in osteoporotic mice. In conclusion, asiatic acid might inhibit oxidative stress and promote osteogenic differentiation through activating SIRT1/FOXO1 to attenuate HFD-induced osteoporosis in mice.
Open Access
Atherosclerosis and oxidative stress
(Murcia : F. Hernández, 2008) Bonomini, F.; Tengattini, S.; Fabiano, A.; Bianchi, R.; Rezzani, R.
This review focuses on the morphological features of atherosclerosis and the involvement of oxidative stress in the initiation and progression of this disease. There is now consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein in the vascular wall. Reactive oxygen species (ROS) are key mediators of signaling pathways that underlie vascular inflammation in atherogenesis, starting from the initiation of fatty streak development, through lesion progression, to ultimate plaque rupture. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction and stroke. Many data support the notion that ROS released from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, myeloperoxidase (MPO), xanthine oxidase (XO), lipoxygenase (LO), nitric oxide synthase (NOS) and enhanced ROS production from dysfunctional mitochondrial respiratory chain, indeed, have a causatory role in atherosclerosis and other vascular diseases. Moreover, oxidative modifications in the arterial wall can contribute to the arteriosclerosis when the balance between oxidants and antioxidants shifts in favour of the former. Therefore, it is important to consider sources of oxidants in the context of available antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase and transferases thiol-disulfide oxidoreductases and peroxiredoxins. Here, we review also the mechanisms in which they are involved in order to accelerate the pace of the discovery and facilitate development of novel therapeutic approaches.
Embargo
Biomarkers of oxidative stress in saliva of sheep: Analytical performance and changes after an experimentally induced stress
(Elsevier, 2019-04) Peres Rubio, Camila; Contreras-Aguilar, Maria Dolores; Quiles, A.; López-Arjona, Marina; Cerón, J.J.; Martínez-Subiela, Silvia; Hevia, M.L.; Escribano Tortosa, Damián; Tecles, Fernando; Medicina y Cirugía Animal
Oxidative stress can affect animal's health and the quality of its final products. The oxidative status can be evaluated by the measurement of both oxidant and antioxidant biomarkers. The use of saliva as a sample is preferable to blood, as individuals with limited training can collect it easily and non-invasively with minimal stress to the animal. The aim of this study was to perform an analytical validation of automated assays of the ferric reducing ability of plasma (FRAP), the cupric reducing antioxidant capacity (CUPRAC), the Trolox equivalent antioxidant capacity (TEAC) and uric acid as antioxidant biomarkers and of the advanced oxidation protein products (AOPP) and hydrogen peroxide (H2O2) as oxidant biomarkers in saliva samples of sheep, and to evaluate their possible changes after stress induced by shearing. All assays produced acceptable results in the analytical validation, from which it can be concluded that oxidative stress biomarkers such as FRAP, CUPRAC, TEAC, uric acid and AOPP and H2O2 can be measured in sheep saliva. In addition, acute stress due to shearing could produce an oxidative stress response in sheep and subsequently increase antioxidants in order to protect cells from damage.
Open Access
Caracterización del pulmón como órgano diana de la muerte por sumersión: evaluación del estrés oxidativo y concentraciones de elementos traza
(Universidad de Murcia, 2022-09-28) Barrera Pérez, Estefanía; María Dolores Pérez Cárceles; Agustín Sibón Olano; Escuela Internacional de Doctorado
El diagnóstico de asfixia por sumersión sigue siendo una de las muertes más difíciles y controvertidas de establecer. Representa una de las principales causas de muerte no intencional a nivel mundial. En la mayoría de las ocasiones, el patólogo forense precisa para llegar a un diagnóstico certero, no solo de los hallazgos de autopsia, sino de una serie de pruebas complementarias tales como estudios histopatológicos, biológicos y químicos. A pesar de ser el pulmón el órgano más afectado en la muerte por sumersión, existe poca información sobre el impacto que tiene en este órgano este tipo de muerte. Los objetivos de nuestro trabajo fue investigar la concentración de elementos traza en los pulmones de sujetos que habían fallecido por diferentes causas de muerte para evaluar la capacidad de discriminación de los elementos traza en el diagnóstico de la muerte por sumersión en agua salada. Y conocer los procesos de estrés oxidativo en las muertes por sumersión en agua salada y otras causas de muerte, analizando los niveles de marcadores de estrés oxidativo (MDA y GSH) en lóbulos pulmonares, así como su correlación con alteraciones en la expresión inmunohistoquímica de la proteína A del surfactante pulmonar. Material y métodos: se analizaron un total de 11 elementos traza en 74 casos forenses mediante Espectrometría de Masas con Plasma Acoplado Inductivamente (ICP-MS). Para identificar alteraciones ultraestructurales y determinar los niveles de elementos traza en las muestras de pulmón se utilizó microscopía electrónica de barrido asociado a espectroscopia de rayos X de dispersión de energía. Por otra parte, estudiamos en una serie de 93 casos de autopsias forenses, los marcadores de estrés oxidativo mediante determinación colorimétrica de Malondialdehído (MDA), por espectrofotometría el GSH (método de Tiztze). Por último, para evaluar la expresión inmunohistoquímica de la PS-A se realizaron análisis histológicos utilizando el anticuerpo monoclonal de ratón anti-SPA humano PE-10. Resultados: se obtuvieron concentraciones significativamente más altas de Br y Sr, y concentraciones significativamente más bajas de Cu, Zn, Se, Cd y Pb en los casos de muerte por sumersión en agua salada frente a otras causas de muerte. Estos resultados fueron confirmados por PCA, que reveló una amplia separación entre las muertes por sumersión y el resto de las causas de muerte. Los niveles de MDA fueron superiores en ambos pulmones en los casos de muerte por sumersión en agua de mar en comparación con otras causas de muerte, existiendo diferencias estadísticamente significativas en las concentraciones de MDA entre los tres grupos de causas de muerte analizados. Del mismo modo, se observó niveles significativamente superiores de GSH en los casos de sumersión frente al resto de muertes, resultando ser más significativo en el pulmón derecho. Se obtuvo mayor expresión inmunohistoquímica de la SP-A en los casos de sumersión en agua salada que en las otras causas de muerte, siendo los niveles superiores en ambos pulmones. En el análisis de correlación entre los niveles de estrés oxidativo (MDA y GSH) en tejido pulmonar y el nivel de expresión de la SP-A se obtuvieron resultados positivos y significativos para los casos de sumersión en agua de mar, tanto en membrana alveolar como en el espacio alveolar. Conclusiones: la determinación de los elementos traza Br y Sr en pulmón junto con la determinación de los niveles de MDA y GSH en tejido pulmonar, así como el nivel de expresión de la SP-A puede ser de gran importancia en el diagnóstico de la muerte por sumersión en agua salada y circunstancias de la muerte. Un mejor conocimiento de la fisiología de la sumersión es importante por sus posibles repercusiones en la adopción de medidas en el abordaje de pacientes que han sobrevivido a un proceso de sumersión y también crucial en patología forense para una interpretación más correcta de los acontecimientos que conducen a la muerte por sumersión.
Open Access
Cathepsin-B dependent autophagy ameliorates steatoheaptitis in chronic exercise rats
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Guo, Rui; Yu, Qian; Liong, Emily C.; Fung, Man Lung; Tipoe, George L.
Purpose. This study aimed to investigate the role of cathepsin B dependent autophagy induced by chronic aerobic exercise on a high-fat diet (HFD)- induced nonalcoholic steatohepatitis (NASH) in rats. Methods. Healthy female (Sprague-Dawley) SD rats (8- 10 weeks old; 180g-200g; n=6 per group) were divided into: (1) control group; (2) HFD group; (3) Exercise group; (4) HFD + exercise group. Rats were fed with a normal chow or an HFD for 12 weeks. Rats with exercise ran on a rotarod for 30 min per day from weeks 9-12. Results. Exercise training significantly (1) upregulated the levels of autophagy markers Beclin1, ATG5 and LC3II partly through inhibiting the p- AKT/mTOR pathway; (2) ameliorated HFD-mediated accumulation of fat mass by upregulating β-oxidation regulator PPAR-α and downregulating fatty acid synthesis marker SREBP-1c via lipophagy; (3) diminished the HFD-induced hepatic pro-inflammatory mediators TNF-α and IL-1β via NF-κB inactivation; (4) decreased the NASH-induced hepatic apoptotic marker caspase-3 activation caused by the upstream oxidative stress and by cytochrome P450 2E1 (CYP2E1); (5) mitigated the HFD-mediated lysosomal membrane permeabilisation and cathepsin B release partly via the reduction of reactive oxygen species (ROS). Conclusions. Chronic aerobic exercise reduces oxidative stress/ROS and ROS may cause lysosomal membrane destabilisation and disrupts the autophagic process. The beneficial effect of chronic exercise may further inhibit the process of lysosome membrane permeabilisation and facilitate lysosome fusion with autophagosomes to trigger autophagy. This process may possibly contribute to the inhibition of cathepsin B released into cytosol which further reduces inflammation and mitochondrial- dependent apoptosis.
Embargo
Changes in mitochondrial membrane composition and oxidative status during rapid growth, maturation and aging in zebrafish, Danio rerio
(Elsevier, 2014-04-24) Almaida Pagán, Pedro Francisco; Lucas-Sanchez, A; Tocher, D R; Fisiología
Considering membranes and membrane components as possible pacemakers of the main processes taking place inside mitochondria, changes in phospholipids or fatty acids could play a central role linking different mechanisms involved in cumulative damage to cell molecules and dysfunction during periods of high stress, such as rapid growth and aging. Changes affecting either lipid class or fatty acid compositions could affect phospholipid and membrane properties and alter mitochondrial function and cell viability. In the present study, mitochondrial oxidative status and mitochondrial membrane phospholipid compositions were analyzed throughout the lifecycle of zebrafish. TBARS content significantly increased in 18-month-old fish while aconitase activity decreased in 24-month-old fish, which have been related with oxidative damage to molecules. Mitochondria-specific superoxide dismutase decreased in 24-month-old animals although this change was not statistically significant. Age affected both mitochondrial phospholipid content and the peroxidation index of most phospholipid classes suggesting that oxidative damage to mitochondrial lipids was occurring.
Embargo
Changes in tissue and mitochondrial membrane composition during rapid growth, maturation and aging in rainbow trout, Oncorhynchus mykiss
(Elsevier, 2012-01-16) Almaida Pagán, Pedro Francisco; Costa, J. de; Mendiola, P; Tocher, D R; Fisiología; Institute of Aquaculture, School of Natural Sciences, University of Stirling, Stirling FK9 4LA, Scotland, United Kingdom; Department of Physiology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain
Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging processes, especially during phases of high oxidative stress that result in molecular damage. In the present study, liver and mitochondrial membrane phospholipid (PL) compositions were analyzed in rainbow trout during its four first years of life, a period characterized by rapid growth and high oxidative stress. Specifically, farmed fish of three ages (1-, 2- and 4-years) were studied, and PL compositions of whole liver and liver mitochondria, and fatty acid compositions of individual PL classes were determined. Liver mitochondrial membranes showed a PL composition different to that of the whole tissue suggesting adaptation of cell and subcellular membranes to specific functions. Individual PL had characteristic fatty acid compositions that were similar in whole liver and mitochondrial membranes. Whole liver and mitochondria showed increased lipid peroxidation with age along with changes in membrane PL fatty acid compositions. Most PL classes showed similar changes in fatty acid composition among the age groups, with reduced proportions of docosahexaenoic acid (DHA) and, generally, concomitantly increased levels of monounsaturated fatty acids, which together resulted in reduced peroxidation index (PIn). However, total polyunsaturated fatty acid (PUFA) content did not change significantly with age due to increased eicosapentaenoic acid, docosapentaenoic acid and, in most PL, increased n−6 PUFA. These results suggest there may be oxidation of PL DHA with compensatory mechanisms to maintain membrane fluidity and function. However, modification of fatty acid composition of specific PLs, such as cardiolipin, could affect the electron transport chain efficiency and propagate the oxidative reaction throughout the cell. In addition, both the content and fatty acid composition of sphingomyelin, which has been suggested as a possible mediator of cell dysfunction and apoptosis, changed with age differently to the other PL classes. Moreover, these changes showed different trends between mitochondria and whole liver. These data suggest there is marked oxidative stress associated with rapid growth and maturation in rainbow trout. Changes observed in membrane lipids point to their possible participation in the processes involved in this species response to oxidative stress and damage accumulation rate.
Open Access
Changes of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure
(BioMed Central (BMC), 2020-11-10) Peres Rubio, Camila; Saril, A.; Kocaturk, M.; Tanaka, R.; Koch, J.; Cerón, J.J.; Yilmaz, Z.; Medicina y Cirugía Animal
Background: Heart failure (HF) is associated with changes in inflammatory and oxidative stress biomarkers. This study aimed to evaluate the changes of a panel of inflammatory and oxidative stress biomarkers in dogs with different stages of HF and its relation with the severity of the disease and echocardiographic changes. A total of 29 dogs with HF as a result of myxomatous mitral valve degeneration or dilated cardiomyopathy were included and classified as stage-A (healthy), B (asymptomatic dogs), C (symptomatic dogs) and D (dogs with end-stage HF) according to the ACVIM staging system. In these dogs an ecnhocardiographic examination was performed and cytokines, and inflammatory and oxidative stress markers were evaluated in serum. Results: KC-like was significantly increased in dogs of stage-C (P<0.01) and -D (P < 0.05) compared with stage-A and -B. Stage-D dogs showed significantly higher serum CRP and Hp (P < 0.05) but lower serum antioxidant capacity (PON1, TEAC, CUPRAC, and thiol) compared to stage-A and -B (P < 0.05). After the treatment, serum levels of CRP, Hp and KClike decreased and serum antioxidant levels increased compared to their pre-treatment values. Left ventricular dimension and LA/Ao ratio correlated positively with CRP, MCP-1, and KC-like but negatively with PON1, GM-CSF, IL-7 and antioxidant biomarkers (P < 0.01). Conclusion: Our results showed that dogs with advanced HF show increases in positive acute-phase proteins and selected inflammatory cytokines such as KC-like, and decreases in antioxidant biomarkers, indicating that inflammation and oxidative stress act as collaborative partners in the pathogenesis of HF. Some of these biomarkers of inflammation and oxidative stress could have the potential to be biomarkers to monitor the severity of the disease and the effect of treatment.
Embargo
Circadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon
(Taylor and Francis Group, Taylor and Francis, 2012-07-23) Baño-Otalora, Beatriz; Popovic, Natalija; Gambini, Juan; Popovic, Miroljub; Viña, José; Bonet-Costa, Vicent; Reiter, Russel J.; Camello, Pedro Javier; Rol, María Ángeles; Madrid, Juan Antonio; Anatomía Humana y Psicobiología
Alzheimer disease (AD) is a neurodegenerative disorder that primarily causes β-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mouse model of AD. To test if melatonin MT1/MT2 receptor activation, alone, was involved, the authors chronically treated some mice with the selective MT1/MT2 receptor agonist ramelteon. The results indicate that many of the circadian and behavioral parameters measured, including oxidative stress markers, were not significantly affected in these AD mice. During the day, though, Tg controls (Tg-CON) showed significantly higher mean activity and body temperature (BT) than wild-type (WT) mice. Overall, BT rhythm amplitude was significantly lower in Tg than in WT mice. Although melatonin treatment had no effect, ramelteon significantly reduced the amplitude of the BT rhythm in Tg mice. Towards the end of the experiment, Tg mice treated with ramelteon (Tg-RAM) showed significantly higher circadian rhythm fragmentation than Tg-CON and reduced circadian BT rhythm strength. The free-running period (τ) for the BT and locomotor activity (LA) rhythms of Tg-CON was <24 h. Whereas melatonin maintained τ at 24 h for BT and LA in both genotypes, ramelteon treatment had no effect. In the behavioral tests, the number of approaches and time spent exploring novel objects were significantly higher in Tg-CON than WT controls. Brain tissue analysis revealed significant reduction in hippocampal protein oxidation in Tg-MEL and Tg-RAM compared with Tg-CON animals. These results suggest that not all aspects of the circadian system are affected in the APPswe/PS1 mice. Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin and ramelteon in this mouse model of AD.
Open Access
Consumption of commonly used artificial food dyes increases activity and oxidative stress in the animal model Caenorhabditis elegans
(Elsevier, 2023-05-02) Guerrero Rubio, M. Alejandra; Hernández García, Samanta; García-Carmona, Francisco; Gandía Herrero, Fernando; Bioquímica y Biología Molecular A
In recent decades, the consumption of artificial colorants in foods and beverages has increased despite of concerns in the general population raised by studies that have shown possible injurious effects. In this study, tartrazine, sunset yellow, quinoline yellow, ponceau 4R, carmoisine and allura red were employed as pure compounds to explore their effects in vivo in the animal model Caenorhabditis elegans. The exposition of C. elegans to these artificial dyes produced damage related with aging such as oxidative stress and lipofuscin accumulation, as well as a heavy shortening of lifespan, alterations in movement patterns and alterations in the production of dopamine receptors. Besides, microarray analysis performed with worms treated with tartrazine and ponceau 4R showed how the consumption of synthetic colorants is able to alter the expression of genes involved in resistance to oxidative stress and neurodegeneration.
Open Access
Cytoglobin-expressing cells in the splenic cords contribute to splenic fibrosis in cirrhotic patients
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Iimuro, Yuji; Yada, Akito; Okada, Toshihiro; Nakamura, Ikuo; Suzumura, Kazuhiro; Xu, Jinyang; Sudo, Makoto; Nishiguchi, Shuhei; Kawada, Norifumi; Hatano, Etsuro; Fujimoto, Jiro
Background and Aim. Among several noninvasive evaluation methods of portal hypertension (PH), the measurement of spleen stiffness is a reliable method for predicting esophageal variceal bleeding; however, the underlying mechanisms for increased stiffness remain unclear. We attempted to elucidate the pathological changes to the spleen and the underlying mechanisms in patients with PH. Methods. Histological examination was performed using splenic tissues from 42 patients with PH who underwent laparoscopic splenectomy, and the results were compared with those from patients without PH. Results. In addition to splenic sinus congestion, diffuse fibrosis was detected in the splenic cords in the red pulp of patients with PH. The degree of the fibrosis was well correlated with severity in thrombocytopenia and splenomegaly. Cells expressing α-smooth muscle actin dramatically increased in the splenic cord. Cytoglobin (Cygb) expression was detected in human splenic cords as reported in animal reticular cells, and fluorescent double immunostaining revealed that these cells expressed α-smooth muscle actin in patients with PH, suggesting transformation of Cygb-expressing cells to myofibroblastic cells. Expression levels of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 2, nitrotyrosine, and transforming growth factor- β were markedly upregulated in the red pulp of patients with PH, implying a significant role of oxidative stress in the mechanism for splenic fibrosis. Conclusion. Splenic fibrosis progresses along with advancement of PH. Cygb-expressing cells in the splenic cord possibly participate in this process through mechanisms including oxidative stress.
Open Access
Efectividad de la suplementación nutricional con polifenoles sobre el daño muscular y marcadores de estrés oxidativo en diferentes tipos de ejercicios físicos: Una revisión dela literatura
(Universidad de Murcia, Servicio de Publicaciones, 2022) Donadio, Pedro; Muñoz, Cristobal; Flores-Lucero, Francisca; Garcia-Diaz, Diego F.; Farias-Valenzuela, Claudio; Quezada, Esteban; Poblete-Aro, Carlos
Durante la realización de ejercicio, existe un desbalance redox que aumenta las especies reactivas de oxígeno generando un estrés oxidativo que favorece el daño muscular incidiendo en el rendimiento físico y deportivo. Diferentes suplementos antioxidantes han sido utilizados para optimizar la recuperación muscular posterior a la realización de ejercicio físico. Sin embargo, los efectos de diversos antioxidantes han sido contraproducentes, ya que las especies reactivas de oxígeno generadas por el ejercicio son necesarias para la adaptación muscular y la disminución de éstas,impide la correcta señalización intracelular y con esto,la adaptación del músculo esquelético frente al ejercicio físico. Los polifenoles son un tipo de antioxidantes que están presentes en diversos frutos y extractos de hierbas que poseen diversas características dependiendo de su estructura y composición, presentando algunos una ruta deseñalización celular similar al ejerciciofísico, generando diferentes estímulos a nivel del músculo esquelético, pudiendo reducir el daño oxidativo generado por el ejercicio e incluso, pudiendo potenciar sus efectos. El objetivo de la presente revisión ala literatura es determinar y describir el efecto de diversos polifenoles en el daño muscular y marcadores de estrés oxidativo posterior a diferentes modalidades de ejercicio físico y deportes en adultos.
Open Access
Effect of endogenous sulfur dioxide in regulating cardiovascular oxidative stress
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Zhu, Mingzhu; Du, Junbao; Liu, Angie Dong; Holmberg, Lukas; Tang, Chaoshu; Jin, Hongfang
In the middle of the 1980s, nitric oxide received extensive attention because of its significant effects in life science. Then, carbon monoxide and hydrogen sulfide were discovered to be gasotransmitters playing important roles in regulating cellular homeostasis. As a common air pollutant, sulfur dioxide (SO2) can cause great harm to the human body by producing free radicals, which causes oxidative damage to various organs. Recently, endogenous SO2 was found to be produced in the cardiovascular system and might be a bioactive molecule regulating the physiological activities including cardiovascular oxidative stress.
Open Access
Effect of NAC treatment and physical activity on neuroinflammation in subchronic Parkinsonism; is physical activity essential?
(BMC, 2018-11-26) Gil Martínez, Ana Luisa; Cuenca Bermejo, Lorena; Sánchez, Consuelo; Estrada Esteban, Cristina; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad; Anatomía Humana y Psicobiología
Background: Neuroprotective strategies are becoming relevant to slow down dopaminergic cell death and inflammatory processes related to the progressive neurodegeneration in Parkinson's disease (PD). Interestingly, among others, physical activity (PA) or anti-oxidant agents (such as N-acetyl-L-cysteine, NAC) are common therapeutic strategies. Therefore, this study aims to analyze if there is a synergistic effect of physical activity along with NAC treatment on dopaminergic degeneration and neuroinflammatory response in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism model after subchronic intoxication. Methods: To ascertain this possibility, 48 8-week-old male mice (C57BL/6 strain) were used. Twenty four of them were placed individually in cages where voluntary physical activity was automatically monitored during 30 days and were divided into groups: (i) control; (ii) NAC; (iii) MPTP, and (iv) MPTP+NAC. The other 24 mice were divided into the same four groups but without physical activity. Results: The data collected during the treatment period showed that there was an overall increase in the total running distance in all groups under physical activity, including Parkinsonian animals. However, the monitoring data per day showed that the activity routine by MPTP and MPTP+NAC groups was disrupted by alterations in the circardian rhythm because of MPTP intoxication. Results from post-mortem studies in the substantia nigra pars compacta (SNpc) showed significant decrease in the number of TH+ cells in all MPTP groups. Moreover, TH+ expression in the striatum was significantly decreased in all MPTP groups. Thus, PA + NAC treatment do not protect dopaminergic neurons against a subchronic intoxication of MPTP. Regarding glial response, the results obtained from microglial analysis do not show significant increase in the number of Iba-1+ cell in MPTP+NAC and MPTP+PA + NAC. In the striatum, a significant decrease is observed only in the MPTP+NAC group compared with that of the MPTP group. The microglial results are reinforced by those obtained from the analysis of astroglial response, in which a decrease in the expression of GFAP+ cells are observed in MPTP+NAC and MPTP+PA + NAC compared with MPTP groups both in the SNpc and in the striatum. Finally, from the study of the astroglial response by the co-localization of GFAP/S100b, we described some expression patterns observed based on the severity of the damage produced by the MPTP intoxication in the different treated groups. Conclusions: These results suggest that the combination of physical activity with an anti-oxidant agent does not have a synergistic neuroprotective effect in the nigrostriatal pathway. Our results show a potential positive effect, only due to NAC treatment, on the neuroinflammatory response after subchronic MPTP intoxication. Thus, physical activity is not essential, under these conditions. However, we believe that physical activity, used for therapeutic purposes, has a beneficial long-term effect. In this line, these results open the door to design longer studies to demonstrate its promising effect as neuroprotective strategy.
Open Access
Effect of tempol on myocardial vascular remodeling in female spontaneously hypertensive rats
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Bonacasa Fernández, Bárbara; Hernández Albaladejo, Inmaculada; Fenoy Palacios, Francisco José; Quesada Pérez, Tomás; López Cano, Bernardo; Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Fisiología
Objective: The present study evaluated whether the treatment with the superoxide anion dismutase mimetic tempol prevents the worsening in hypertension and in myocardial vascular remodeling induced by ovariectomy in female spontaneously hypertensive rats (SHR). Methods: Experiments were performed in ten week old female SHRs randomly assigned to the groups: intact (INT: given vehicle; INT+T: treated with tempol, 90 mg/kg/day), ovariectomized (OVX: vehicle and OVX+T: tempol, respectively) and ovariectomized treated with 17ß-estradiol (OVX+E2 and OVX+E2+T). Evolution of systolic blood pressure (SBP) was determined every other week in lightly restrained awake rats using a noninvasive computerized tail-cuff plethysmography system. At 18 weeks of age the heart was excised and structural changes in histopathological sections of coronary vessels were quantified on a computerized imaging system analyzer. Results: SBP was significantly lower in female SHRs treated with tempol compared to the values measured in untreated animals. In the vascular remodeling of myocardial arterioles, OVX+T rats had a lower media cross sectional area and media-to-lumen ratio than those observed in the OVX SHR. Interestingly, treatment with tempol in the presence of estradiol (in female INT and OVX+E2 SHR ) increased media cross sectional area and wall-to-lumen ratio of myocardial arterioles, despite the fact that it lowered arterial pressure in those groups. Conclusions: These results indicate that tempol prevents arterial hypertension and blunts myocardial vascular remodeling in ovariectomized SHR. Paradoxically, when tempol is given in presence of estradiol it has a detrimental effect on myocardial arteriolar remodeling
Open Access
Effects of catecholaminergic nerve lesion on endometrial development during early pregnancy in mice
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Dong, Yulan; Liu, Guanhui; Wang, Zixu; Li, Jing; Cao, Jing; Chen, Yaoxing
Maternal stress is common during pregnancy and the postnatal period. This stress typically activates the sympathetic nervous system which releases catecholamines. This study explored the influence of sympathectomy by using neurotoxin 6-hydroxydopamine (6-OHDA) on embryo implantation, and investigated the influence mechanism of sympathectomy on reconstruction of endometrial structure during early pregnancy. In the 6-OHDA-treated mice, uterine glands in the endometrium developed poorly, and the gland epithelia were arranged irregularly during early pregnancy. Furthermore, vacuoles, karyopykosis and plasmarrhexis appeared in some gland epithelia. The percentage of uterine glands and the density of proliferating cell nuclear antigen (PCNA) positivity were dramatically decreased, and Fas ligand (FasL) expression was decreased in cells from pregnancy days 5-9 (E5-9) in the treated group. Antioxidant enzyme activity levels in uteri were lower but the malondialdehyde (MDA) levels were higher in the 6- OHDA mice than those in the control mice at E5-9. Similarly, the number of inducible nitric oxide synthase (iNOS) positive cells was significantly increased during early pregnancy following treatment with 6-OHDA. Our results have indicated that peripheral catecholaminergic nerve lesions induced by 6-OHDA cause adverse pregnancy outcomes through disruption of endometrial gland development, which increases oxidative stress and iNOS expression in the endometrium. Thus, catecholaminergic nerves might favourably influence blastocyst implantation, foetal survival and development during early pregnancy by oxidative state regulation and endometrial gland reconstruction.