Aging impairs neurogenic contraction in guinea pig urinary bladder: role of oxidative stress and melatonin

2007 ◽  
Vol 293 (2) ◽  
pp. R793-R803 ◽  
Author(s):  
Pedro J. Gómez-Pinilla ◽  
Maria J. Pozo ◽  
Pedro J. Camello
Keyword(s):  
Oxidative Stress ◽  
Urinary Bladder ◽  
Guinea Pig ◽  
Electrical Field Stimulation ◽  
Neuromuscular Function ◽  
Melatonin Treatment ◽  
Age Related ◽  
Afferent Fibers ◽  
Bladder Disorders ◽  
The Impact

The incidence of urinary bladder disturbances increases with age, and free radical accumulation has been proposed as a causal factor. Here we investigated the association between changes in bladder neuromuscular function and oxidative stress in aging and the possible benefits of melatonin treatment. Neuromuscular function was assessed by electrical field stimulation (EFS) of isolated guinea pig detrusor strips from adult and aged female guinea pigs. A group of adult and aged animals were treated with 2.5 mg·kg−1·day−1 melatonin for 28 days. Neurotransmitter blockers were used to dissect pharmacologically the EFS-elicited contractile response. EFS induced a neurogenic and frequency-dependent contraction that was impaired by aging. This impairment is in part related to a decrease in detrusor myogenic contractility. Age also decreased the sensitivity of the contraction to pharmacological blockade of purinergic and sensitive fibers but increased the effect of blockade of nitrergic and adrenergic nerves. The density of cholinergic and nitrergic nerves remained unaltered, but aging modified afferent fibers. These changes were associated with an increased level of markers for oxidative stress. Melatonin treatment normalized oxidative levels and counteracted the aging-associated changes in bladder neuromuscular function. In conclusion, these results show that aging modifies neurogenic contraction and the functional profile of the urinary bladder plexus and simultaneously increases the oxidative damage to the organ. Melatonin reduces oxidative stress and improves the age-induced changes in bladder neuromuscular function, which could be of importance in reducing the impact of age-related bladder disorders.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

scholarly journals Brain Ageing, Cognition and Diet: A Review of the Emerging Roles of Food-Based Nootropics in Mitigating Age-related Memory Decline

2019 ◽  
Vol 12 (1) ◽  
pp. 2-14 ◽  
Author(s):  
Adejoke Yetunde Onaolapo ◽  
Adebimpe Yemisi Obelawo ◽  
Olakunle James Onaolapo
Keyword(s):  
Oxidative Stress ◽  
Cognitive Decline ◽  
Antioxidant Defense System ◽  
Food Ingredients ◽  
Memory Decline ◽  
Age Related ◽  
Brain Ageing ◽  
Nootropic Agents ◽  
Age Related Cognitive Decline ◽  
The Impact

Background: Age-related cognitive decline has been suggested to result from an increase in the brain neuron loss, which is attributable to continued derangement of the brain’s oxidant/ antioxidant balance. Increased oxidative stress and a concomitant decrease in the brain’s antioxidant defense system have been associated with functional senescence and organismal ageing. However, nature has configured certain foods to be rich sources of nootropic agents, with research showing that increased consumption of such foods or food ingredients may be protective against ageing-related memory decline. This knowledge is becoming increasingly valuable in an era when the boundary that separates food from medicine is becoming blurred. In this review, we examine extant literature dealing with the impact of ageing on brain structure and function, with an emphasis on the roles of oxidative stress. Secondly, we review the benefits of food-based antioxidants with nootropic effects and/or food-based nootropic agents in mitigating memory decline; with a view to improving our understanding of likely mechanisms. We also highlight some of the limitations to the use of food-based nootropics and suggest ways in which they can be better employed in the clinical management of age-related cognitive decline. Conclusion: While it is known that the human brain endures diverse insults in the process of ageing, food-based nootropics are likely to go a long way in mitigating the impacts of these insults. Further research is needed before we reach a point where food-based nootropics are routinely prescribed.

scholarly journals Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-24 ◽  
Author(s):  
Mika Reinisalo ◽  
Anna Kårlund ◽  
Ali Koskela ◽  
Kai Kaarniranta ◽  
Reijo O. Karjalainen
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Damage ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Age Related ◽  
Cellular Defence ◽  
The Impact ◽  
Stilbene Compounds

Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer’s disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2) mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed.

scholarly journals Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2346
Author(s):  
Aline Yammine ◽  
Amira Zarrouk ◽  
Thomas Nury ◽  
Anne Vejux ◽  
Norbert Latruffe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Expression Level ◽  
Cholesterol Oxidation ◽  
Mrna Levels ◽  
Antioxidant Genes ◽  
Dietary Polyphenols ◽  
N2a Cells ◽  
Age Related ◽  
The Impact

The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death. When associated with RSV, QCT and API (3.125; 6.25 µM), 7KC-induced toxicity was reduced. The ability of QCT, RSV and API to prevent 7KC-induced oxidative stress was characterized by a decrease in reactive oxygen species (ROS) production in whole cells and at the mitochondrial level; by an attenuation of the increase in the level and activity of catalase; by attenuating the decrease in the expression, level and activity of glutathione peroxidase 1 (GPx1); by normalizing the expression, level and activity of superoxide dismutases 1 and 2 (SOD1, SOD2); and by reducing the decrease in the expression of nuclear erythroid 2-like factor 2 (Nrf2) which regulates antioxidant genes. QCT, RSV and API also prevented mitochondrial dysfunction in 7KC-treated cells by counteracting the loss of mitochondrial membrane potential (ΨΔm) and attenuating the decreased gene expression and/or protein level of AMP-activated protein kinase α (AMPKα), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) implicated in mitochondrial biogenesis. At the peroxisomal level, QCT, RSV and API prevented the impact of 7KC by counteracting the decrease in ATP binding cassette subfamily D member (ABCD)3 (a peroxisomal mass marker) at the protein and mRNA levels, as well as the decreased expresssion of genes associated with peroxisomal biogenesis (Pex13, Pex14) and peroxisomal β-oxidation (Abcd1, Acox1, Mfp2, Thiolase A). The 7KC-induced decrease in ABCD1 and multifunctional enzyme type 2 (MFP2), two proteins involved in peroxisomal β-oxidation, was also attenuated by RSV, QCT and API. 7KC-induced cell death, which has characteristics of apoptosis (cells with fragmented and/or condensed nuclei; cleaved caspase-3; Poly(ADP-ribose) polymerase (PARP) fragmentation) and autophagy (cells with monodansyl cadaverine positive vacuoles; activation of microtubule associated protein 1 light chain 3–I (LC3-I) to LC3-II, was also strongly attenuated by RSV, QCT and API. Thus, in N2a cells, 7KC induces a mode of cell death by oxiapoptophagy, including criteria of OXIdative stress, APOPTOsis and autoPHAGY, associated with mitochondrial and peroxisomal dysfunction, which is counteracted by RSV, QCT, and API reinforcing the interest for these polyphenols in prevention of diseases associated with increased 7KC levels.

scholarly journals Metabolomic profiling of serum in aging mice supplemented with tocotrienol-rich fraction for identification of female reproductive aging biomarkers

2018 ◽  
Vol 14 (4) ◽  
pp. 467-470
Author(s):  
Norrabiátul Adawiyah Aziz ◽  
Fathimah Mohamad ◽  
Teh Lay Kek ◽  
Nuraliza Abdul Satar
Keyword(s):  
Oxidative Stress ◽  
Ovarian Function ◽  
Corn Oil ◽  
Negative Impact ◽  
Protective Mechanism ◽  
Reproductive Aging ◽  
Cell Stage ◽  
Age Related ◽  
Tocotrienol Rich Fraction ◽  
The Impact

Ovarian aging has been associated with increased oxidative stress leading to loss of ovarian function and infertility. Tocotrienol, a potent antioxidant, has been proven to exert beneficial effects in the female reproductive system. Serum metabolites were analyzed to examine the biochemical changes and to identify biomarkers related to reproductive aging that could lead to poor embryo quality and development. Female Mus musculus mice were divided into four groups. Six-month-old mice were given tocopherol-stripped corn oil as a vehicle control while other groups were supplemented orally with tocotrienol-rich fraction (TRF) at doses of 90, 120, and 150 mg/kg bodyweight for two months, respectively. After two months, mice from all groups were super ovulated, and euthanized. Embryos were collected at the 2-cell stage and cultured to monitor their development while serum was used for metabolomic analysis. The percentage of normal embryos and development of embryos to blastocyst stage were significantly higher in groups supplemented with TRF. A total of 71 metabolites that are related to reproductive aging were identified in all groups and significant changes were detected in metabolic pathways that include fatty acids, amino acids metabolism and steroid hormone biosynthesis. These changes suggest that aging has a negative impact on cellular energy storage, energy metabolism and oxidative stress that subsequently affect female fertility. Supplementation with TRF prevented the impact of age related metabolic changes on the embryo. Thus, it appears that TRF exerts a protective mechanism towards female reproductive aging.

scholarly journals Anti-Apoptosis and Autophagy Effects of Melatonin Protect Rat Chondrocytes against Oxidative Stress via Regulation of AMPK/Foxo3 Pathways

Cartilage ◽  
2021 ◽  
pp. 194760352110387
Author(s):  
Zhaoxun Chen ◽  
Chen Zhao ◽  
Pengcheng Liu ◽  
Haohan Huang ◽  
Shuhong Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blotting ◽  
Redox Homeostasis ◽  
Cartilage Degeneration ◽  
Cell Counting ◽  
Autophagic Flux ◽  
Sprague Dawley ◽  
Melatonin Treatment ◽  
Age Related

Objective Emerging evidence has indicated that excessive reactive oxygen species (ROS) have detrimental effects on osteoarthritis (OA). This study aimed to elucidate the effects of melatonin (MT), an antioxidant indolamine secreted from the pineal gland, on chondrocyte senescence and cartilage degeneration, thereby clarifying the underlying mechanisms of ROS-induced OA pathogenesis. Design Hydrogen peroxide (H2O2) was used to induce oxidative stress in rat chondrocytes. ROS levels were evaluated using cytometry and immunofluorescence. Cell viability was detected using the Cell Counting Kit-8 (CCK-8) assay. Western blotting and qPCR (Quantiative Real-Time Polymerase Chain Reaction) were used to examine apoptosis and autophagy. For in vivo experiments, male Sprague-Dawley rats were randomly divided into a sham-operated group, DMM (destabilization of the medial meniscus) surgery group, and surgery groups that received melatonin. Knee joints were collected and stained for histological analysis. Results The data demonstrated that melatonin treatment significantly suppressed H2O2-induced matrix degradation and apoptosis, and maintained mitochondrial redox homeostasis. In addition, an enhancement of autophagic flux was observed through western blotting. These findings corresponded with activation of the AMPK/Foxo3 signaling pathways upon melatonin treatment. Histological staining and transmission electron microscopy (TEM) micrographs also demonstrated that melatonin alleviated cartilage ossification and chondrocyte hypertrophy in vivo. Conclusions Our results indicated that melatonin protected chondrocytes via mitochondrial redox homeostasis and autophagy. The effects of melatonin on senescence may apply to other age-related diseases. Thus, melatonin may have multiple potential therapeutic applications.

Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD+-CD38 Axis

2021 ◽  
pp. 1-16
Author(s):  
Bing Si Li ◽  
Ri Zhe Zhu ◽  
Seok-Hee Lim ◽  
Jae Ho Seo ◽  
Byung-Min Choi
Keyword(s):  
Oxidative Stress ◽  
Cellular Senescence ◽  
Lung Diseases ◽  
Molecular Mechanisms ◽  
Driving Mechanism ◽  
Dependent Manner ◽  
Aging Effects ◽  
Chronic Lung Diseases ◽  
Age Related ◽  
The Impact

Oxidative stress-induced cellular senescence is now regarded as an important driving mechanism in chronic lung diseases-particularly chronic obstructive pulmonary disease (COPD). 4′,5,7-trihydroxyflavone (Apigenin) is a natural flavonoid product abundantly present in fruits, vegetables, and Chinese medicinal herbs. It has been known that apigenin has anti-oxidant, anti-inflammatory and liver-protecting effects. The efficacy of apigenin for lung aging, however, has not been reported. In this study, we selected the hydrogen peroxide (H2O[Formula: see text]- or doxorubicin (DOXO)-induced senescence model in WI-38 human embryonic lung fibroblast cells to determine the potential anti-aging effects of apigenin in vitro and associated molecular mechanisms. We found that apigenin reduced senescence-associated [Formula: see text]-galactosidase (SA-[Formula: see text]-gal) activity and promoted cell growth, concomitant with a decrease in levels of Acetyl (ac)-p53, p21[Formula: see text], and p16[Formula: see text] and an increase in phospho (p)-Rb. Apigenin also increased the activation ratio of silent information regulator 1 (SIRT1), nicotinamide adenine dinucleotide (NAD[Formula: see text], and NAD[Formula: see text]/NADH and inhibited cluster of differentiation 38 (CD38) activity in a concentration-dependent manner. SIRT1 inhibition by SIRT1 siRNA abolished the anti-aging effect of apigenin. In addition, CD38 inhibition by CD38 siRNA or apigenin increased the SIRT1 level and reduced H2O2-induced senescence. Our findings suggest that apigenin is a promising phytochemical for reducing the impact of senescent cells in age-related lung diseases such as COPD.

scholarly journals Age-Related Oxidative Changes in Primary Porcine Fibroblasts Expressing Mutated Huntingtin

2019 ◽  
Vol 19 (1) ◽  
pp. 22-34
Author(s):  
Petra Smatlikova ◽  
Georgina Askeland ◽  
Michaela Vaskovicova ◽  
Jiri Klima ◽  
Jan Motlik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Nuclear Dna ◽  
Neurodegenerative Disorder ◽  
Cyclin B1 ◽  
Gene Encoding ◽  
Proliferation Capacity ◽  
Mitochondrial Superoxide ◽  
Age Related ◽  
The Impact

Background: Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by CAG triplet expansions in the huntingtin gene. Oxidative stress is linked to HD pathology, although it is not clear whether this is an effect or a mediator of disease. The transgenic (TgHD) minipig expresses the N-terminal part of human-mutated huntingtin and represents a unique model to investigate therapeutic strategies towards HD. A more detailed characterization of this model is needed to fully utilize its potential. Methods: In this study, we focused on the molecular and cellular features of fibroblasts isolated from TgHD minipigs and the wild-type (WT) siblings at different ages, pre-symptomatic at the age of 24–36 months and with the onset of behavioural symptoms at the age of 48 months. We measured oxidative stress, the expression of oxidative stress-related genes, proliferation capacity along with the expression of cyclin B1 and D1 proteins, cellular permeability, and the integrity of the nuclear DNA (nDNA) and mitochondrial DNA in these cells. Results: TgHD fibroblasts isolated from 48-month-old animals showed increased oxidative stress, which correlated with the overexpression of SOD2 encoding mitochondrial superoxide dismutase 2, and the NEIL3 gene encoding DNA glycosylase involved in replication-associated repair of oxidized DNA. TgHD cells displayed an abnormal proliferation capacity and permeability. We further demonstrated increased nDNA damage in pre-symptomatic TgHD fibroblasts (isolated from animals aged 24–36 months). Conclusions: Our results unravel phenotypic alterations in primary fibroblasts isolated from the TgHD minipig model at the age of 48 months. Importantly, nDNA damage appears to precede these phenotypic alterations. Our results highlight the impact of fibroblasts from TgHD minipigs in studying the molecular mechanisms of HD pathophysiology that gradually occur with age.

scholarly journals Anti-Inflammatory and Anti-Oxidative Synergistic Effect of Vitamin D and Nutritional Complex on Retinal Pigment Epithelial and Endothelial Cell Lines against Age-Related Macular Degeneration

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1423
Author(s):  
Maria Hernandez ◽  
Sergio Recalde ◽  
Jorge González-Zamora ◽  
Valentina Bilbao-Malavé ◽  
Manuel Sáenz de Viteri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Macular Degeneration ◽  
Oxidative Dna Damage ◽  
Retinal Pigment ◽  
Photoreceptor Cells ◽  
Age Related Macular Degeneration ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by dysfunction of retinal pigmented epithelial (RPE) and loss of photoreceptor cells under oxidative stress and inflammatory conditions. Vitamin D and antioxidants have beneficial effects against retinal degenerative diseases, such as AMD. We investigated the impact of associating vitamin D (ND) with a nutritional antioxidant complex (Nutrof Total®; N) on oxidative stress and inflammation-like induced conditions by H2O2 and LPS, respectively, in human retinal epithelial (ARPE-19) and human retinal endothelial (HREC) cells. Application of either N or ND treatments to H2O2-induced media in ARPE-19 cells counteracted late apoptosis, attenuated oxidative DNA damage, and increased cell proliferation. Significant reduction in the expression levels of MCP1, IL-8, and IL6 cytokines was observed following application of either N or ND treatments under LPS-induced conditions in ARPE-19 cells and in MCP-1 and IL12p70 cytokine levels in HREC cells. ND and not N revealed significant downregulation of IFNγ in ARPE-19 cells, and of IL-6 and IL-18 in HREC cells. In conclusion, adding vitamin D to Nutrof Total® protects in a synergistic way against oxidative and inflammatory stress-induced conditions in retinal epithelial and endothelial cells.

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