Browsing by Subject "antioxidants"
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Item Alzheimer's Fibroblasts are More Susceptible to Oxidative Stress(2001-05-01) Marshall, Pamela L.; Neeraj Agarwal; Robert GracyMarshall, Pamela L., Alzheimer’s Fibroblasts Are More Susceptible to Oxidative Stress. Master’s of Science (Biomedical Sciences). May 2001. Recent evidence indicates that oxidative stress contributes to neuronal death in Alzheimer’s disease (AD). In addition, it has been suggested that AD is a systemic illness in which the development of the disease is only visible in the brain. The aim of this research is to develop experimental procedures using a simple cell model, the fibroblast, to determine if proteins derived from AD skin fibroblasts are more sensitive to oxidation by reactive oxygen species than non-AD cells, and to assess the ability of antioxidants to prevent this oxidative damage in AD fibroblasts. Preliminary findings suggest that changes in sensitivity are already detectable in fibroblasts from AD patients, probably as a consequence of genetic component as well as other risk factors. Therefore, this biochemical marker might have the potential for identifying individuals at risk for AD.Item Antioxidants, Exercise, APOE Genotype and Brain Function(2014-12-01) Chaudhari, Kiran; Nathalie Sumien; Michael J. Forster; Eric B. GonzalesApolipoprotein E4 (APOE4) is a well-established and extensively prevalent genetic risk factor for the development of Alzheimer’s disease (AD). The presence of APOE4 allele accelerates the pathophysiology and symptomology of AD. A large set (36%) of the population suffering from AD expresses APOE4. Being a chronic progressive disease with very few pharmaco-therapeutic agents approved by FDA, non-drug lifestyle modifications have been an important part of management of AD. People often eat healthy diet rich in antioxidants and focus on healthy living habits such as exercise. Health care providers frequently suggest combining antioxidants with physical activity for higher benefits. Antioxidants have been beneficial in counteracting oxidative stress and improving learning and memory. Similarly, different regimens of exercise also improved cognition and delayed development of AD. However, the nature of the interaction between antioxidants and exercise remain elusive and complicated. While some studies reported additive effects, others have also shown a concerning antagonistic action of the antioxidants on the beneficial effects of exercise. In the context of APOE genotype, we set our study to determine the nature of such interaction between antioxidants and exercise. Using vitamins C and E and a treadmill-based forced exercise in a genetically modified mouse model expressing human APOE3 and APOE4 (GFAP-APOE3, GFAP-APOE4), we explored the nature of that interaction on functional and biochemical outcomes. We examined the mice for spatial learning and memory, working memory and executive function, coordinated running performance, muscular reflexes, spontaneous locomotor activity, anxiety and muscle strength. Interestingly, we observed that the young adult mice expressing E4 allele performed better on higher brain functions including spatial learning and memory and short term memory in contrast to middle age mice, which developed a cognitive deficit as expected. Motor functions, reflexes and coordination were poor among all the mice carrying E4 allele irrespective of age. Antioxidants and exercise interventions led to outcomes that were dependent on genotype, age and the brain function under consideration. There was additive beneficial effect of combination of antioxidants and exercise on cognitive outcomes but not on motor outcomes in middle age groups. However, in young adults, an antagonistic interaction was observed on motor outcomes but no such interaction was observed on cognitive outcomes. Hence we can conclude that, combination of antioxidants and exercise is not a “fit for all” approach and needs to be tailored base on individual’s age and genotype.Item ApoE Genotype-Dependent Response to Antioxidant and Exercise Interventions on Brain Function(MDPI, 2020-06-25) Chaudhari, Kiran; Wong, Jessica M.; Vann, Philip H.; Como, Tori; O'Bryant, Sid E.; Sumien, NathalieThis study determined whether antioxidant supplementation is a viable complement to exercise regimens in improving cognitive and motor performance in a mouse model of Alzheimer's disease risk. Starting at 12 months of age, separate groups of male and female mice expressing human Apolipoprotein E3 (GFAP-ApoE3) or E4 (GFAP-ApoE4) were fed either a control diet or a diet supplemented with vitamins E and C. The mice were further separated into a sedentary group or a group that followed a daily exercise regimen. After 8 weeks on the treatments, the mice were administered a battery of functional tests including tests to measure reflex and motor, cognitive, and affective function while remaining on their treatment. Subsequently, plasma inflammatory markers and catalase activity in brain regions were measured. Overall, the GFAP-ApoE4 mice exhibited poorer motor function and spatial learning and memory. The treatments improved balance, learning, and cognitive flexibility in the GFAP-ApoE3 mice and overall the GFAP-ApoE4 mice were not responsive. The addition of antioxidants to supplement a training regimen only provided further benefits to the active avoidance task, and there was no antagonistic interaction between the two interventions. These outcomes are indicative that there is a window of opportunity for treatment and that genotype plays an important role in response to interventions.Item Comparative Proteomics Analysis Reveals Unique Early Signaling Response of Saccharomyces cerevisiae to Oxidants with Different Mechanism of Action(MDPI, 2020-12-26) Pandey, Prajita; Zaman, Khadiza; Prokai, Laszlo; Shulaev, VladimirThe early signaling events involved in oxidant recognition and triggering of oxidant-specific defense mechanisms to counteract oxidative stress still remain largely elusive. Our discovery driven comparative proteomics analysis revealed unique early signaling response of the yeast Saccharomyces cerevisiae on the proteome level to oxidants with a different mechanism of action as early as 3 min after treatment with four oxidants, namely H2O2, cumene hydroperoxide (CHP), and menadione and diamide, when protein abundances were compared using label-free quantification relying on a high-resolution mass analyzer (Orbitrap). We identified significant regulation of 196 proteins in response to H2O2, 569 proteins in response to CHP, 369 proteins in response to menadione and 207 proteins in response to diamide. Only 17 proteins were common across all treatments, but several more proteins were shared between two or three oxidants. Pathway analyses revealed that each oxidant triggered a unique signaling mechanism associated with cell survival and repair. Signaling pathways mostly regulated by oxidants were Ran, TOR, Rho, and eIF2. Furthermore, each oxidant regulated these pathways in a unique way indicating specificity of response to oxidants having different modes of action. We hypothesize that interplay of these signaling pathways may be important in recognizing different oxidants to trigger different downstream MAPK signaling cascades and to induce specific responses.Item INTERACTION OF APOE GENOTYPE, ANTIOXIDANTS AND EXERCISE ON BRAIN FUNCTION.(2014-03) Chaudhari, Kiran; Wong, Jessica M.; Vann, Philip H.; Sumien, NathalieHuge rise in the incidence of azheimer's disease is projected with baby boomers' retiring age. There are very few drugs in market to manage this condition. Doctors and care takers often depend on the lifestyle modification to assist the definitive drug therapy. Most common form of lifestyle modification is exercise and diet rich in antioxidants. Further, APOE4 is a gene that is commonly expressed and a well established genetic risk factor for Alzheimer's development. We identified role of gender and APOE4 in affecting the benefits of lifestyle modification. We used a mouse model that express human APOE4 and develops memory loss at early age. This model is routinely used for alzheimer's disease related experiments. We treated these mice with treadmill based exercise and fed them with diet rich in antioxidants like vitamin C and vitamin E. After treatment these mice were tested for learning and memory abilities using interesting and non stressful techniques that involve swimming, running on rotating rod etc. We found that exercise and antioxidants are more beneficial in combination in only some of the tests. The benefits of the combination of exercise and antioxidants depends on sex, APOE genotype and age of the mouse. Purpose (a): The ε4 allele of apolipoprotein E (ApoE) has been associated with increased risk for the development of late-onset Alzheimer’s disease (AD). To prevent or reduce the appearance of brain dysfunction, a healthy lifestyle, such as exercising and eating antioxidants, is often recommended. Physical activity has been shown to have an allele-specific beneficial effect on cognition in humans and rodents. Antioxidant therapy is often suggested to improve brain function, as increased oxidative stress has been correlated with brain dysfunction, especially in ε4 carriers. Health conscious individuals are likely to combine exercise with antioxidant intake to increase protection; however recent studies have indicated a potential negative interaction of these two factors. In some cases, antioxidant intake abolished the beneficial effects of exercise. Our study aimed at determining the nature of the interaction between exercise and antioxidants on functional outcomes in a model of increased AD risk. Methods (b): Male and female mice (12month), expressing the human ApoE3 or E4, were placed under one of the treatment: Sedentary/control diet (SedCon), Sedentary /antioxidant-rich diet (Vitamins E-195mg/kg body weight/day and C-287mg/kg body weight/day; SedEC), Exercise/control diet (ExCon), Exercise/ antioxidant-rich diet (ExEC), for 8 weeks prior to behavioral testing including coordinated running (rotorod), spatial learning and memory (Morris water maze) and discriminated avoidance (T-maze). Results (c): Overall, ApoE3 mice performed better than ApoE4 mice on the rotorod test and ExEC treatment improved the performance of the male ApoE3 only. The ExEC treatment improved spatial learning in both male and female ApoE4 mice, whereas ExCon improved performance only in the ApoE4 females. Maximum spatial learning was improved with ExEC in males regardless of genotype but only in the ApoE3 females. In the discriminated avoidance task, initial learning was improved with ExCon treatment in ApoE3 mice regardless of gender. Cognitive flexibility was improved by ExEC treatment in ApoE3 male and female and in ApoE4 females but not in male ApoE4. Conclusions (d): These results indicate that genotype and sex are critical determinants in the functional outcomes of the treatment regimens.Item Modulation of Mitochondrial Metabolic Parameters and Antioxidant Enzymes in Healthy and Glaucomatous Trabecular Meshwork Cells with Hybrid Small Molecule SA-2(MDPI, 2023-07-29) Amankwa, Charles E.; Young, Olivia; DebNath, Biddut; Gondi, Sudershan R.; Rangan, Rajiv; Ellis, Dorette Z.; Zode, Gulab S.; Stankowska, Dorota L.; Acharya, SuchismitaOxidative stress (OS)-induced mitochondrial damage is a risk factor for primary open-angle glaucoma (POAG). Mitochondria-targeted novel antioxidant therapies could unearth promising drug candidates for the management of POAG. Previously, our dual-acting hybrid molecule SA-2 with nitric oxide-donating and antioxidant activity reduced intraocular pressure and improved aqueous humor outflow in rodent eyes. Here, we examined the mechanistic role of SA-2 in trabecular meshwork (TM) cells in vitro and measured the activity of intracellular antioxidant enzymes during OS. Primary human TM cells isolated from normal (hNTM) or glaucomatous (hGTM) post-mortem donors and transformed glaucomatous TM cells (GTM-3) were used for in vitro assays. We examined the effect of SA-2 on oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro using Seahorse Analyzer with or without the oxidant, tert-butyl hydroperoxide (TBHP) treatment. Concentrations of total antioxidant enzymes, catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPx) were measured. We observed significant protection of both hNTM and hGTM cells from TBHP-induced cell death by SA-2. Antioxidant enzymes were elevated in SA-2-treated cells compared to TBHP-treated cells. In addition, SA-2 demonstrated an increase in mitochondrial metabolic parameters. Altogether, SA-2 protected both normal and glaucomatous TM cells from OS via increasing mitochondrial energy parameters and the activity of antioxidant enzymes.Item Neuroprotection of Cyperus esculentus L. orientin against cerebral ischemia/reperfusion induced brain injury(Wolters Kluwer - Medknow, 2020-03) Jing, Si-Qun; Wang, Sai-Sai; Zhong, Rui-Min; Zhang, Jun-Yan; Wu, Jin-Zi; Tu, Yi-Xian; Pu, Yan; Yan, Liang-JunOrientin is a flavonoid monomer. In recent years, its importance as a source of pharmacological active substance is growing rapidly due to its properties such as anti-myocardial ischemia, anti-apoptosis, anti-radiation, anti-tumor, and anti-aging. However, the neuroprotective effects of Orientin on stroke injury have not been comprehensively evaluated. The aim of the present study was thus to investigate the neuroprotective capacity and the potential mechanisms of Cyperus esculentus L. orientin (CLO) from Cyperus esculentus L. leaves against ischemia/reperfusion (I/R) injury using standard orientin as control. For in vitro studies, we treated HT22 cells with CoCl2 as an in vitro ischemic injury model. HT22 cells in the control group were treated with CoCl2. For in vivo studies, we used rat models of middle cerebral artery occlusion, and animals that received sham surgery were used as controls. We found that CLO protected CoCl2-induced HT22 cells against ischemia/reperfusion injury by lowering lipid peroxidation and reactive oxygen species formation as well as decreasing protein oxidation. However, CLO did not reduce the release of lactate dehydrogenase nor increase the activity of superoxide dismutase. Results showed that CLO could decrease neurological deficit score, attenuate brain water content, and reduce cerebral infarct volume, leading to neuroprotection during cerebral ischemia-reperfusion injury. Our studies indicate that CLO flavonoids can be taken as a natural antioxidant and bacteriostastic substance in food and pharmaceutical industry. The molecular mechanisms of CLO could be at least partially attributed to the antioxidant properties and subsequently inhibiting activation of casepase-3. All experimental procedures and protocols were approved on May 16, 2016 by the Experimental Animal Ethics Committee of Xinjiang Medical University of China (approval No. IACUC20160516-57).