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  1. Chia TY, Murugaiyah V, Khan NA, Sattar MA, Abdulla MH, Johns EJ, et al.
    Physiol Res, 2021 03 17;70(1):13-26.
    PMID: 33728924
    Reactive oxygen species (ROS) such as superoxide (O2-) generated by NAD(P)H oxidases have emerged as important molecules in blood pressure regulation. This study investigated the effect of apocynin and catalase on blood pressure and renal haemodynamic and excretory function in an L-NAME induced hypertension model. Forty Male Wistar-Kyoto (WKY) rats (n=8 per group) were treated with either: vehicle (WKY-C); L-NAME (WKY-L, 15 mg/kg/day in drinking fluid); WKY-L given apocynin to block NAD(P)H oxidase (WKY-LApo, 73 mg/kg/day in drinking water.); WKY-L given catalase to enhance ROS scavenging (WKY-LCat, 10000 U/kg/day i.p.); and WKY-L receiving apocynin plus catalase (WKY-LApoCat) daily for 14 days. L-NAME elevated systolic blood pressure (SBP), 116+/-1 to 181±4 mmHg, reduced creatinine clearance, 1.69+/-0.26 to 0.97+/-0.05 ml/min/kg and fractional sodium excretion, 0.84+/-0.09 to 0.55+/-0.09 % at day 14. Concomitantly, plasma malondialdehyde (MDA) increased six fold, while plasma total superoxide dismutase (T-SOD), plasma nitric oxide (NO) and plasma total antioxidant capacity (T-AOC) were decreased by 60-70 % and Nox 4 mRNA expression was increased 2-fold. Treatment with apocynin and catalase attenuated the increase in SBP and improved renal function, enhanced antioxidative stress capacity and reduced the magnitude of Nox4 mRNAs expression in the L-NAME treated rats. This study demonstrated that apocynin and catalase offset the development of L-NAME induced hypertension, renal dysfunction and reduced oxidative stress status, possibly contributed by a reduction in Nox4 expression during NOS inhibition. These findings would suggest that antioxidant compounds such as apocynin and catalase have potential in treating cardiovascular diseases.
    Matched MeSH terms: Reactive Oxygen Species/metabolism*
  2. Jayusman PA, Budin SB, Ghazali AR, Taib IS, Louis SR
    Pak J Pharm Sci, 2014 Nov;27(6):1873-80.
    PMID: 25362611
    Indiscriminate application of organophosphate (OP) pesticides has led to environmental pollution and severe health problems. The aim of the present study was to evaluate the effect of palm oil tocotrienol-rich fraction (TRF) on biochemical and morphological changes of the liver in rats treated with fenitrothion (FNT), a type of OP pesticide. A total of 28 male Sprague-Dawley rats were divided into four groups; control group, TRF-supplemented group, FNT-treated group and TRF+FNT group. TRF (200 mg/kg) was supplemented 30 minutes prior to FNT (20 mg/kg) administration, both orally for 28 consecutive days. Following 28 days of treatment, plasma biochemical changes and liver morphology were evaluated. The body and absolute liver weights were significantly elevated in TRF+FNT group compared to FNT group. TRF administration significantly decreased the total protein level and restored the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in TRF + FNT group. In contrast, total bilirubin level, γ-glutamyltranferase (GGT) and cholinesterase activity in TRF + FNT group did not significantly differ from FNT group. Administration of TRF also prevented FNT-induced morphological changes of liver as observed by electron microscope. In conclusion, TRF supplementation showed potential protective effect towards biochemical and ultrastructural changes in liver induced by FNT.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  3. Bandyopadhyay A, Ping FW, Keong CC
    J Hum Ergol (Tokyo), 2011 Dec;40(1-2):63-72.
    PMID: 25665208 DOI: 10.11183/jhe.40.63
    Acute supplementation of Panax ginseng (PG) is known not to impose any significant effect on endurance performance of recreational Malaysian runners, while caffeine augments the ergogenic property of some herbs. The present study was aimed to examine the effects of acute supplementation of caffeine and PG on endurance running performance in a hot and humid condition. Nine heat adapted Malaysian recreational runners (age : 25.4 ± 6.9 years, body mass : 57.6 ± 8.4 kg; body height : 168.3 ± 7.6 cm) ingested either placebo or combined dose of 5 mg x kg(-1) of body weight of caffeine and 200 mg of PG one hour before the running on treadmill at 70% of VO2(max) in this placebo-controlled double blind randomised study in a laboratory environment of 31 degrees C and 70% relative humidity. They drank 3 ml x kg(-1) of body weight of cool water every 20 minutes during the exercise to prevent dehydration. Blood samples were withdrawn and oxygen uptake was recorded every 20 minutes while heart rate, core body temperature, skin temperature and ratings of perceived exertion (RPE) were recorded every 10 minutes during the trials. Endurance time was significantly different (P < 0.05) between experimental and placebo trials. Heart rate, skin temperature, core body temperature, oxygen uptake, RPE, plasma insulin, glucose, free fatty acid and lactate levels during the endurance exercise did not show any significant difference between the trials. Thus, we conclude that combined and acute supplementation of caffeine and PG in the said doses improved the endurance running performance of the heat-adapted male recreational runners.
    Matched MeSH terms: Oxygen/blood
  4. Guarini G, Kiyooka T, Ohanyan V, Pung YF, Marzilli M, Chen YR, et al.
    Basic Res Cardiol, 2016 May;111(3):29.
    PMID: 27040114 DOI: 10.1007/s00395-016-0547-4
    Mitochondrial dysfunction in obesity and diabetes can be caused by excessive production of free radicals, which can damage mitochondrial DNA. Because mitochondrial DNA plays a key role in the production of ATP necessary for cardiac work, we hypothesized that mitochondrial dysfunction, induced by mitochondrial DNA damage, uncouples coronary blood flow from cardiac work. Myocardial blood flow (contrast echocardiography) was measured in Zucker lean (ZLN) and obese fatty (ZOF) rats during increased cardiac metabolism (product of heart rate and arterial pressure, i.v. norepinephrine). In ZLN increased metabolism augmented coronary blood flow, but in ZOF metabolic hyperemia was attenuated. Mitochondrial respiration was impaired and ROS production was greater in ZOF than ZLN. These were associated with mitochondrial DNA (mtDNA) damage in ZOF. To determine if coronary metabolic dilation, the hyperemic response induced by heightened cardiac metabolism, is linked to mitochondrial function we introduced recombinant proteins (intravenously or intraperitoneally) in ZLN and ZOF to fragment or repair mtDNA, respectively. Repair of mtDNA damage restored mitochondrial function and metabolic dilation, and reduced ROS production in ZOF; whereas induction of mtDNA damage in ZLN reduced mitochondrial function, increased ROS production, and attenuated metabolic dilation. Adequate metabolic dilation was also associated with the extracellular release of ADP, ATP, and H2O2 by cardiac myocytes; whereas myocytes from rats with impaired dilation released only H2O2. In conclusion, our results suggest that mitochondrial function plays a seminal role in connecting myocardial blood flow to metabolism, and integrity of mtDNA is central to this process.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  5. Mat Rosly M, Mat Rosly H, Hasnan N, Davis GM, Husain R
    Eur J Phys Rehabil Med, 2017 Aug;53(4):527-534.
    PMID: 28092144 DOI: 10.23736/S1973-9087.17.04456-2
    BACKGROUND: Current strategies for increased physical activity and exercise in individuals with spinal cord injury (SCI) face many challenges with regards to maintaining their continuity of participation. Barriers cited often include problems with accessing facilities, mundane, monotonous or boring exercises and expensive equipment that is often not adapted for wheelchair users.

    AIM: To compare the physiological responses and user preferences between conventional heavy-bag boxing against a novel form of video game boxing, known as exergaming boxing.

    DESIGN: Cross-sectional study.

    SETTING: Exercise laboratory setting in a university medical center.

    POPULATION: Seventeen participants with SCI were recruited, of which sixteen were male and only one female. Their mean age was 35.6±10.2 years.

    METHODS: All of them performed a 15-minute physical exercise session of exergaming and heavy-bag boxing in a sitting position. The study assessed physiological responses in terms of oxygen consumption, metabolic equivalent (MET) and energy expenditure between exergaming and heavy-bag boxing derived from open-circuit spirometry. Participants also rated their perceived exertion using Borg's category-ratio ratings of perceived exertion.

    RESULTS: Both exergaming (MET: 4.3±1.0) and heavy-bag boxing (MET: 4.4±1.0) achieved moderate exercise intensities in these participants with SCI. Paired t-test revealed no significant differences (P>0.05, Cohen's d: 0.02-0.49) in the physiological or perceived exertional responses between the two modalities of boxing. Post session user survey reported all the participants found exergaming boxing more enjoyable.

    CONCLUSIONS: Exergaming boxing, was able to produce equipotent physiological responses as conventional heavy-bag boxing. The intensity of both exercise modalities achieved recommended intensities for health and fitness benefits.

    CLINICAL REHABILITATION IMPACT: Exergaming boxing have the potential to provide an enjoyable, self-competitive environment for moderate-vigorous exercise even at the comfort of their homes.

    Matched MeSH terms: Oxygen Consumption/physiology
  6. Kalid N, Zaidan AA, Zaidan BB, Salman OH, Hashim M, Albahri OS, et al.
    J Med Syst, 2018 Mar 02;42(4):69.
    PMID: 29500683 DOI: 10.1007/s10916-018-0916-7
    This paper presents a new approach to prioritize "Large-scale Data" of patients with chronic heart diseases by using body sensors and communication technology during disasters and peak seasons. An evaluation matrix is used for emergency evaluation and large-scale data scoring of patients with chronic heart diseases in telemedicine environment. However, one major problem in the emergency evaluation of these patients is establishing a reasonable threshold for patients with the most and least critical conditions. This threshold can be used to detect the highest and lowest priority levels when all the scores of patients are identical during disasters and peak seasons. A practical study was performed on 500 patients with chronic heart diseases and different symptoms, and their emergency levels were evaluated based on four main measurements: electrocardiogram, oxygen saturation sensor, blood pressure monitoring, and non-sensory measurement tool, namely, text frame. Data alignment was conducted for the raw data and decision-making matrix by converting each extracted feature into an integer. This integer represents their state in the triage level based on medical guidelines to determine the features from different sources in a platform. The patients were then scored based on a decision matrix by using multi-criteria decision-making techniques, namely, integrated multi-layer for analytic hierarchy process (MLAHP) and technique for order performance by similarity to ideal solution (TOPSIS). For subjective validation, cardiologists were consulted to confirm the ranking results. For objective validation, mean ± standard deviation was computed to check the accuracy of the systematic ranking. This study provides scenarios and checklist benchmarking to evaluate the proposed and existing prioritization methods. Experimental results revealed the following. (1) The integration of TOPSIS and MLAHP effectively and systematically solved the patient settings on triage and prioritization problems. (2) In subjective validation, the first five patients assigned to the doctors were the most urgent cases that required the highest priority, whereas the last five patients were the least urgent cases and were given the lowest priority. In objective validation, scores significantly differed between the groups, indicating that the ranking results were identical. (3) For the first, second, and third scenarios, the proposed method exhibited an advantage over the benchmark method with percentages of 40%, 60%, and 100%, respectively. In conclusion, patients with the most and least urgent cases received the highest and lowest priority levels, respectively.
    Matched MeSH terms: Oxygen/blood
  7. Jaudan A, Sharma S, Malek SNA, Dixit A
    PLoS One, 2018;13(2):e0191523.
    PMID: 29420562 DOI: 10.1371/journal.pone.0191523
    Pinostrobin (PN) is a naturally occurring dietary bioflavonoid, found in various medicinal herbs/plants. Though anti-cancer potential of many such similar constituents has been demonstrated, critical biochemical targets and exact mechanism for their apoptosis-inducing actions have not been fully elucidated. The present study was aimed to investigate if PN induced apoptosis in cervical cancer cells (HeLa) of human origin. It is demonstrated that PN at increasing dose effectivity reduced the cell viability as well as GSH and NO2- levels. Condensed nuclei with fragmented chromatin and changes in mitochondrial matrix morphology clearly indicated the role of mitochondria in PN induced apoptosis. A marked reduction in mitochondrial membrane potential and increased ROS production after PN treatment showed involvement of free radicals, which in turn further augment ROS levels. PN treatment resulted in DNA damage, which could have been triggered by an increase in ROS levels. Decrease in apoptotic cells in the presence of caspase 3 inhibitor in PN-treated cells suggested that PN induced apoptosis via caspase dependent pathways. Additionally, a significant increase in the expression of proteins of extrinsic (TRAIL R1/DR4, TRAIL R2/DR5, TNF RI/TNFRSF1A, FADD, Fas/TNFRSF6) and intrinsic pathway (Bad, Bax, HTRA2/Omi, SMAC/Diablo, cytochrome C, Pro-Caspase-3, Cleaved Caspase-3) was observed in the cells exposed to PN. Taken together, these observations suggest that PN efficiently induces apoptosis through ROS mediated extrinsic and intrinsic dependent signaling pathways, as well as ROS mediated mitochondrial damage in HeLa cells.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  8. Hussain RM, Abdullah NF, Amom Z
    J Integr Med, 2016 Nov;14(6):456-464.
    PMID: 27854197 DOI: 10.1016/S2095-4964(16)60279-0
    OBJECTIVE: This study investigated the effects of allylpyrocatechol (APC), the major component in ethanolic extract of Piper betle, on key oxidative stress resistance enzymes important for the survival of Staphylococcus aureus, a major pathogen in the human host.

    METHODS: Effects of APC on expressions of genes encoding catalase (katA), superoxide dismutases (SODs), including sodA and sodM, and alkyl hydroperoxide reductase (ahpC) in S· aureus were quantitated by RT-qPCR in reference to gyrA and 16S rRNA. Corresponding activities of the enzymes were also investigated. The Livak analysis was performed for verification of gene-fold expression data. Effects of APC on intracellular and extracellular reactive oxygen species (ROS) levels were determined using the nitroblue tetrazolium (NBT) reduction assay.

    RESULTS: APC-treated S· aureus cells had higher sodA and sodM transcripts at 1.5-fold and 0.7-fold expressions respectively with corresponding increase in total SOD activity of 12.24 U/mL compared to untreated cells, 10.85 U/mL (P<0.05). Expression of ahpC was highest in APC-treated cells with 5.5-fold increased expression compared to untreated cells (P<0.05). Correspondingly, ahpC activity was higher in APC-treated cells at 0.672 (A310nm) compared to untreated cells which was 0.394 (A310nm). In contrast, katA expression was 1.48-fold and 0.33-fold lower respectively relative to gyrA and 16S rRNA. Further, APC-treated cells showed decreased catalase activity of 1.8 ×10-4 (U/L or μmol/(min·L)) compared to untreated cells, which was 4.8 ×10-4 U/L (P<0.05). Absorbance readings (A575nm) for the NBT reduction assay were 0.709 and 0.695 respectively for untreated and treated cells, which indicated the presence of ROS. APC-treated S· aureus cells had lower ROS levels both extracellularly and intracellularly, but larger amounts remained intracellularly compared to extracellular levels with absorbances of 0.457 and 0.137 respectively (P<0.05).

    CONCLUSION: APC induced expressions of both sodA and sodM, resulting in increased total SOD activity in S· aureus. Higher sodA expression indicated stress induced intracellularly involving O2- , presumably leading to higher intracellular pools of H2O2. A concommittant decrease in katA expression and catalase activity possibly induced ahpC expression, which was increased the highest in APC-treated cells. Our findings suggest that in the absence of catalase, cells are propelled to seek an alternate pathway involving ahpC to reduce stress invoked by O2- and H2O2. Although APC reduced levels of ROS, significant amounts eluded its antioxidative action and remained intracellularly, which adds to oxidative stress in treated cells.

    Matched MeSH terms: Reactive Oxygen Species/metabolism
  9. Ganapathy R, Mani S, Hanumanth Rao BR, Tunku K, Ray B, Bhat A, et al.
    Front Biosci (Elite Ed), 2018 03 01;10:437-448.
    PMID: 29293467
    Thraatchathi Chooranam (TC), is a polyphenol-rich Indian traditional medicine. Present study was undertaken to investigate the effects of TC against H2O2 induced oxidative stress and apoptotic damage in H9C2 cardiomyocytes. Cell viability assay indicated relative safety (IC50= 488.10±12.04 mg/ml) of TC. Pretreatment of cells with TC upregulated anti-apoptotic Bcl2, and anti-oxidants TRX1 and TRXR and downregulated Bax and HIF-α and inflammatory genes iNOS and TNF-α. Together, these findings show that TC has both anti-oxidant and anti-apoptotic properties. Further studies may be considered to identify the bioactive principle(s) and precise mechanisms of action of TC.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  10. Guerriero G, D'Errico G, Di Giaimo R, Rabbito D, Olanrewaju OS, Ciarcia G
    Environ Sci Pollut Res Int, 2018 Jul;25(19):18286-18296.
    PMID: 28936697 DOI: 10.1007/s11356-017-0098-8
    Important toxicological achievements have been made during the last decades using reptiles. We focus our investigation on gonadal reproductive health of the soil biosentinel Podarcis sicula which is very sensitive to endocrine-disrupting chemicals. The aim of this study is to quantitatively detect, by sensitive microassays, reactive oxygen species and the glutathione antioxidants in the testis and investigate if they are differentially expressed before and after remediation of a site of the "Land of Fires" (Campania, Italy) subject to illicit dumping of unknown material. The oxidative stress level was evaluated by electron spin resonance spectroscopy applying a spin-trapping procedure able to detect products of lipid peroxidation, DNA damage and repair by relative mobility shift, and poly(ADP-ribose) polymerase enzymatic activity, respectively, the expression of glutathione peroxidase 4 transcript by real-time quantitative PCR analysis, the antioxidant glutathione S-transferase, a well-assessed pollution index, by enzymatic assay and the total soluble antioxidant capacity. Experimental evidences from the different techniques qualitatively agree, thus confirming the robustness of the combined experimental approach. Collected data, compared to those from a reference unpolluted site constitute evidence that the reproductive health of this lizard is impacted by pollution exposure. Remediation caused significant reduction of reactive oxygen species and downregulation of glutathione peroxidase 4 mRNAs in correspondence of reduced levels of glutathione S-transferase, increase of antioxidant capacity, and repair of DNA integrity. Taken together, our results indicate directions to define new screening approaches in remediation assessment.
    Matched MeSH terms: Reactive Oxygen Species/metabolism*
  11. Weinberg RP, Koledova VV, Schneider K, Sambandan TG, Grayson A, Zeidman G, et al.
    Sci Rep, 2018 Nov 06;8(1):16423.
    PMID: 30401897 DOI: 10.1038/s41598-018-34763-3
    Neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are becoming more prevalent and an increasing burden on society. Neurodegenerative diseases often arise in the milieu of neuro-inflammation of the brain. Reactive astrocytes are key regulators in the development of neuro-inflammation. This study describes the effects of Palm Fruit Bioactives (PFB) on the behavior of human astrocytes which have been activated by IL-1β. When activated, the astrocytes proliferate, release numerous cytokines/chemokines including TNFα, RANTES (CCL5), IP-10 (CXCL10), generate reactive oxygen species (ROS), and express specific cell surface biomarkers such as the Intercellular Adhesion Molecule (ICAM), Vascular Cellular Adhesion Molecule (VCAM) and the Neuronal Cellular Adhesion Molecule (NCAM). Interleukin 1-beta (IL-1β) causes activation of human astrocytes with marked upregulation of pro-inflammatory genes. We show significant inhibition of these pro-inflammatory processes when IL-1β-activated astrocytes are exposed to PFB. PFB causes a dose-dependent and time-dependent reduction in specific cytokines: TNFα, RANTES, and IP-10. We also show that PFB significantly reduces ROS production by IL-1β-activated astrocytes. Furthermore, PFB also reduces the expression of ICAM and VCAM, both in activated and naïve human astrocytes in vitro. Since reactive astrocytes play an essential role in the neuroinflammatory state preceding neurodegenerative diseases, this study suggests that PFB may have a potential role in their prevention and/or treatment.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  12. Binti Kamaruddin NA, Fong LY, Tan JJ, Abdullah MNH, Singh Cheema M, Bin Yakop F, et al.
    Molecules, 2020 May 29;25(11).
    PMID: 32485974 DOI: 10.3390/molecules25112534
    Endothelial cell injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of cardiovascular diseases. Omentin, an adipocytokine that is abundantly expressed in visceral fat tissue, has been reported to possess anti-inflammatory and antidiabetic properties. However, endothelial protective effects of omentin against oxidative stress remain unclear. This study aimed to evaluate the protective effect of omentin against hydrogen peroxide (H2O2)-induced cell injury in human umbilical vein endothelial cells (HUVECs). Cytotoxicity and cytoprotective effects of omentin were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic activity of HUVECs was detected using Annexin-V/PI and Hoechst 33258 staining methods. Antioxidant activity of omentin was evaluated by measuring both reactive oxygen species (ROS) levels and glutathione peroxidase (GPx) activity. No cytotoxicity effect was observed in HUVECs treated with omentin alone at concentrations of 150 to 450 ng/ml. MTT assay showed that omentin significantly prevented the cell death induced by H2O2 (p < 0.001). Hoechst staining and flow cytometry also revealed that omentin markedly prevented H2O2-induced apoptosis. Moreover, omentin not only significantly inhibited ROS production (p < 0.01) but also significantly (p < 0.01) increased GPx activity in HUVECs. In conclusion, our data suggest that omentin may protect HUVECs from injury induced by H2O2.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  13. Liew HJ, Chiarella D, Pelle A, Faggio C, Blust R, De Boeck G
    PMID: 23921225 DOI: 10.1016/j.cbpa.2013.07.029
    The objective of this study was to investigate the interaction between feeding, exercise and cortisol on metabolic strategies of common carp over a 168h post-implant period. Feeding provided readily available energy and clearly increased muscle and liver protein and glycogen stores. Swimming, feeding and cortisol all induced aerobic metabolism by increasing oxygen consumption, and stimulated protein metabolism as demonstrated by the increased ammonia and urea excretion and ammonia quotient. Hypercortisol stimulated ammonia self-detoxifying mechanisms by enhancing ammonia and urea excretion, especially during severe exercise. At high swimming level, higher branchial clearance rates in cortisol treated fish succeeded in eliminating the elevation of endogenous ammonia, resulting in reduced plasma Tamm levels compared to control and sham implanted fish. Carp easily induced anaerobic metabolism, both during routine and active swimming, with elevated lactate levels as a consequence. Both feeding and cortisol treatment increased this dependence on anaerobic metabolism. Hypercortisol induced both glycogenesis and gluconeogenesis resulting in hyperglycemia and muscle and liver glycogen deposition, most likely as a protective mechanism for prolonged stress situations and primarily fuelled by protein mobilization.
    Matched MeSH terms: Oxygen Consumption*
  14. Wong GR, Mazumdar P, Lau SE, Harikrishna JA
    J Plant Physiol, 2018 Dec;231:219-233.
    PMID: 30292098 DOI: 10.1016/j.jplph.2018.09.018
    Genetic improvement is an important approach for crop improvement towards yield stability in stress-prone areas. Functional analysis of candidate stress response genes can provide key information to allow the selection and modification of improved crop varieties. In this study, the constitutive expression of a banana cDNA, MaRHD3 in Arabidopsis improved the ability of transgenic lines to adapt to drought conditions. Transgenic Arabidopsis plants expressing MaRHD3 had roots with enhanced branching and more root hairs when challenged with drought stress. The MaRHD3 plants had higher biomass accumulation, higher relative water content, higher chlorophyll content and an increase in activity of reactive oxygen species (ROS) scavenging enzymes; SOD, CAT, GR, POD and APX with reduced water loss rates compared to control plants. The analysis of oxidative damage indicated lower cell membrane damage in transgenic lines compared to control plants. These findings, together with data from higher expression of ABF-3 and higher ABA content of drought-stressed transgenic MaRHD3 expressing plants, support the involvement of the ABA signal pathway and ROS scavenging enzyme systems in MaRHD3 mediated drought tolerance.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  15. Huang D, Awad ACA, Tang C, Chen Y
    Environ Toxicol, 2024 Mar;39(3):1335-1349.
    PMID: 37955318 DOI: 10.1002/tox.24036
    BACKGROUND: Demethylnobiletin (DN), with a variety of biological activities, is a polymethoxy-flavanone (PMF) found in citrus. In the present study, we explored the biological activities and potential mechanism of DN to improve cerebral ischemia reperfusion injury (CIRI) in rats, and identified DN as a novel neuroprotective agent for patients with ischemic brain injury.

    METHODS: Rat CIRI models were established via middle cerebral artery occlusion (MCAO). Primary nerve cells were isolated and cultured in fetal rat cerebral cortex in vitro, and oxygen-glucose deprivation/reperfusion (OGD/R) models of primary nerve cells were induced. After intervention with DN with different concentrations in MCAO rats and OGD/R nerve cells, 2,3,5-triphenyltetrazolium chloride staining was used to quantify cerebral infarction size in CIRI rats. Modified neurological severity score was utilized to assess neurological performance. Histopathologic staining and live/dead cell-viability staining was used to observe apoptosis. Levels of glutathione (GSH), superoxide dismutase (SOD), reactive oxygen species (ROS) and malondialdehyde (MDA) in tissues and cells were detected using commercial kits. DN level in serum and cerebrospinal fluid of MCAO rats were measured by liquid chromatography tandem mass spectrometry. In addition, expression levels of proteins like Kelch like ECH associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nfr2) and heme oxygenase 1 (HO-1) in the Nrf2/HO-1 pathway, and apoptosis-related proteins like Cleaved caspase-3, BCL-2-associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) were determined by Western blot and immunofluorescence.

    RESULTS: DN can significantly enhance neurological function recovery by reducing cerebral infarction size and weakening neurocytes apoptosis in MCAO rats. It was further found that DN could improve oxidative stress (OS) injury of nerve cells by bringing down MDA and ROS levels and increasing SOD and GSH levels. Notably, DN exerts its pharmacological influences through entering blood-brain barrier. Mechanically, DN can reduce Keap1 expression while activate Nrf2 and HO-1 expression in neurocytes.

    CONCLUSIONS: The protective effect of DN on neurocytes have been demonstrated in both in vitro and in vivo circumstances. It deserves to be developed as a potential neuroprotective agent through regulating the Nrf2/HO-1 signaling pathway to ameliorate neurocytes impairment caused by OS.

    Matched MeSH terms: Reactive Oxygen Species/metabolism
  16. WHO Solidarity Trial Consortium
    Lancet, 2022 May 21;399(10339):1941-1953.
    PMID: 35512728 DOI: 10.1016/S0140-6736(22)00519-0
    BACKGROUND: The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date.

    METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.

    FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.

    INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).

    FUNDING: WHO.

    Matched MeSH terms: Oxygen/administration & dosage
  17. Sharma N, Singh V, Pandey AK, Mishra BN, Kulsoom M, Dasgupta N, et al.
    Biomolecules, 2019 11 21;9(12).
    PMID: 31766572 DOI: 10.3390/biom9120764
    Nanoparticles (NPs) possessing antibacterial activity represent an effective way of overcoming bacterial resistance. In the present work, we report a novel formulation of a nanoantibiotic formed using Ampicillin/sulbactam (Ams) and a zinc oxide nanoparticle (ZnO NP). 'ZnO NP-Ams' nanoantibiotic formulation is optimized using response surface methodology coupled genetic algorithm approach. The optimized formulation of nanoantibiotic (ZnO NP: 49.9 μg/mL; Ams: 33.6 μg/mL; incubation time: 27 h) demonstrated 15% enhanced activity compared to the unoptimized formulation against K. pneumoniae. The reactive oxygen species (ROS) generation was directly proportional to the interaction time of nanoantibiotic and K. pneumoniae after the initial lag phase of ~18 h as evident from 2'-7'-Dichlorodihydrofluorescein diacetate assay. A low minimum inhibitory concentration (6.25 μg/mL) of nanoantibiotic formulation reveals that even a low concentration of nanoantibiotic can prove to be effective against K. pneumoniae. The importance of nanoantibiotic formulation is also evident by the fact that the 100 μg/mL of Ams and 25 µg of ZnO NP was required individually to inhibit the growth of K. pneumonia, whereas only 6.25 μg/mL of optimized nanoantibiotic formulation (ZnO NP and Ams in the ratio of 49.9: 33.6 in μg/mL and conjugation time of 27 h) was needed for the same.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  18. Yida Z, Imam MU, Ismail M
    PMID: 25475744 DOI: 10.1186/1472-6882-14-468
    Edible birds' nest (EBN) is reported to be antioxidant-rich. However, the fate of its antioxidants after oral consumption is not yet reported. To explore this, we hypothesized that EBN antioxidants are released from their matrix when subjected to in vitro simulated gastrointestinal digestion.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  19. Dhakal S, Kushairi N, Phan CW, Adhikari B, Sabaratnam V, Macreadie I
    Int J Mol Sci, 2019 Oct 14;20(20).
    PMID: 31615073 DOI: 10.3390/ijms20205090
    Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Lewy body dementia, etc. Alzheimer's Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer's Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer's Disease.
    Matched MeSH terms: Reactive Oxygen Species/metabolism
  20. Al-Qubaisi MS, Rasedee A, Flaifel MH, Ahmad SH, Hussein-Al-Ali S, Hussein MZ, et al.
    Int J Nanomedicine, 2013;8:4115-29.
    PMID: 24204141 DOI: 10.2147/IJN.S50061
    The long-term objective of the present study was to determine the ability of NiZn ferrite nanoparticles to kill cancer cells. NiZn ferrite nanoparticle suspensions were found to have an average hydrodynamic diameter, polydispersity index, and zeta potential of 254.2 ± 29.8 nm, 0.524 ± 0.013, and -60 ± 14 mV, respectively. We showed that NiZn ferrite nanoparticles had selective toxicity towards MCF-7, HepG2, and HT29 cells, with a lesser effect on normal MCF 10A cells. The quantity of Bcl-2, Bax, p53, and cytochrome C in the cell lines mentioned above was determined by colorimetric methods in order to clarify the mechanism of action of NiZn ferrite nanoparticles in the killing of cancer cells. Our results indicate that NiZn ferrite nanoparticles promote apoptosis in cancer cells via caspase-3 and caspase-9, downregulation of Bcl-2, and upregulation of Bax and p53, with cytochrome C translocation. There was a concomitant collapse of the mitochondrial membrane potential in these cancer cells when treated with NiZn ferrite nanoparticles. This study shows that NiZn ferrite nanoparticles induce glutathione depletion in cancer cells, which results in increased production of reactive oxygen species and eventually, death of cancer cells.
    Matched MeSH terms: Reactive Oxygen Species/analysis; Reactive Oxygen Species/metabolism
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