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1.
Aquat Toxicol ; 245: 106104, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1693934

ABSTRACT

There have been significant impacts of the current COVID-19 pandemic on society including high health and economic costs. However, little is known about the potential ecological risks of this virus despite its presence in freshwater systems. In this study, we aimed to evaluate the exposure of Poecilia reticulata juveniles to two peptides derived from Spike protein of SARS-CoV-2, which was synthesized in the laboratory (named PSPD-2002 and PSPD-2003). For this, the animals were exposed for 35 days to the peptides at a concentration of 40 µg/L and different toxicity biomarkers were assessed. Our data indicated that the peptides were able to induce anxiety-like behavior in the open field test and increased acetylcholinesterase (AChE) activity. The biometric evaluation also revealed that the animals exposed to the peptides displayed alterations in the pattern of growth/development. Furthermore, the increased activity of superoxide dismutase (SOD) and catalase (CAT) enzymes were accompanied by increased levels of malondialdehyde (MDA), reactive oxygen species (ROS) and hydrogen peroxide (H2O2), which suggests a redox imbalance induced by SARS-CoV-2 spike protein peptides. Moreover, molecular docking analysis suggested a strong interaction of the peptides with the enzymes AChE, SOD and CAT, allowing us to infer that the observed effects are related to the direct action of the peptides on the functionality of these enzymes. Consequently, our study provided evidence that the presence of SARS-CoV-2 viral particles in the freshwater ecosystems offer a health risk to fish and other aquatic organisms.


Subject(s)
COVID-19 , Poecilia , Water Pollutants, Chemical , Acetylcholinesterase/metabolism , Animals , Catalase/metabolism , Ecosystem , Humans , Hydrogen Peroxide , Molecular Docking Simulation , Pandemics , Poecilia/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Superoxide Dismutase/metabolism , Water Pollutants, Chemical/toxicity
2.
Arch Med Res ; 52(8): 843-849, 2021 11.
Article in English | MEDLINE | ID: covidwho-1635366

ABSTRACT

AIM AND BACKGROUND: Covid-19 has been as an important human infectious disease that has affected several countries. Cytokine storm has major role is Covid-19 pathogenesis. The association between inflammation and oxidative stress is well stablished. In this article, we aim to assess oxidative stress markers in Covid-19 patients compare to the healthy subjects. METHOD: A total of 48 persons (24 with Covid-19 and 24 controls) were evaluated in this research. Serum oxidative stress markers including Malondialdehyde (MDA), total oxidant status (TOS), activity of catalase (CAT) and super oxide dismutase (SOD) were measured alongside routine laboratory tests. RESULTS: Patients group were divided into ICU and Non-ICU groups. ESR, CRP and serum level of ferritin were significantly higher in case group. Serum level of albumin was significantly lower in Covid-19 patients. Serum MDA and TOS was significantly increased in Covid-19 patients. Also, Covid-19 patients had higher serum activity of CAT and GPX. CONCLUSION: Oxidative stress markers are significantly elevated in Covid-19 patients. This may have significant role in mechanism of disease development. In the fight against Covid-19, as a global struggle, all possible treatments demand more attention. So, Covid-19 patients may benefit from strategies for reducing or preventing oxidative stress.


Subject(s)
COVID-19 , Antioxidants/metabolism , Catalase/metabolism , Humans , Malondialdehyde , Oxidative Stress , SARS-CoV-2 , Superoxide Dismutase/metabolism
3.
Infect Immun ; 89(12): e0031521, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1575412

ABSTRACT

Mycobacterium tuberculosis is a chronic infectious disease pathogen. To date, tuberculosis is a major infectious disease that endangers human health. To better prevent and treat tuberculosis, it is important to study the pathogenesis of M. tuberculosis. Based on early-stage laboratory research results, in this study, we verified the upregulation of sod2 in Bacillus Calmette-Guérin (BCG) and H37Rv infection. By detecting BCG/H37Rv intracellular survival in sod2-silenced and sod2-overexpressing macrophages, sod2 was found to promote the intracellular survival of BCG/H37Rv. miR-495 then was determined to be downregulated by BCG/H37Rv. BCG/H37Rv can upregulate sod2 expression by miR-495 to promote the intracellular survival of BCG/H37Rv through a decline in ROS levels. This study provides a theoretical basis for developing new drug targets and treating tuberculosis.


Subject(s)
Macrophages/microbiology , Macrophages/physiology , MicroRNAs/genetics , Mycobacterium tuberculosis/physiology , Reactive Oxygen Species/metabolism , Superoxide Dismutase/genetics , Tuberculosis/etiology , Tuberculosis/metabolism , Disease Susceptibility , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Mycobacterium bovis , Superoxide Dismutase/metabolism , Tuberculosis/pathology
4.
Arch Med Res ; 52(8): 843-849, 2021 11.
Article in English | MEDLINE | ID: covidwho-1527582

ABSTRACT

AIM AND BACKGROUND: Covid-19 has been as an important human infectious disease that has affected several countries. Cytokine storm has major role is Covid-19 pathogenesis. The association between inflammation and oxidative stress is well stablished. In this article, we aim to assess oxidative stress markers in Covid-19 patients compare to the healthy subjects. METHOD: A total of 48 persons (24 with Covid-19 and 24 controls) were evaluated in this research. Serum oxidative stress markers including Malondialdehyde (MDA), total oxidant status (TOS), activity of catalase (CAT) and super oxide dismutase (SOD) were measured alongside routine laboratory tests. RESULTS: Patients group were divided into ICU and Non-ICU groups. ESR, CRP and serum level of ferritin were significantly higher in case group. Serum level of albumin was significantly lower in Covid-19 patients. Serum MDA and TOS was significantly increased in Covid-19 patients. Also, Covid-19 patients had higher serum activity of CAT and GPX. CONCLUSION: Oxidative stress markers are significantly elevated in Covid-19 patients. This may have significant role in mechanism of disease development. In the fight against Covid-19, as a global struggle, all possible treatments demand more attention. So, Covid-19 patients may benefit from strategies for reducing or preventing oxidative stress.


Subject(s)
COVID-19 , Antioxidants/metabolism , Catalase/metabolism , Humans , Malondialdehyde , Oxidative Stress , SARS-CoV-2 , Superoxide Dismutase/metabolism
5.
Cells ; 10(9)2021 08 25.
Article in English | MEDLINE | ID: covidwho-1374305

ABSTRACT

According to the neurological symptoms of SARS-CoV-2 infection, it is known that the nervous system is influenced by the virus. We used pediatric human cerebral cortical cell line HCN-2 as a neuronal model of SARS-CoV-2 infection, and, through transcriptomic analysis, our aim was to evaluate the effect of SARS-CoV-2 in this type of cells. Transcriptome analyses revealed impairment in TXN gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in KAT5. Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of CDKN2A and a decrease in CDK4 and CDK6 point to the blocking of the cell cycle that, according to the deregulation of repairing mechanism, has apoptosis as the outcome. A high level of proapoptotic gene PMAIP1 is indeed coherent with neuronal death, as also supported by increased levels of caspase 3. The upregulation of cell-cycle-blocking genes and apoptosis suggests a sufferance state of neurons after SARS-CoV-2 infection, followed by their inevitable death, which can explain the neurological symptoms reported. Further analyses are required to deeply explain the mechanisms and find potential treatments to protect neurons from oxidative stress and prevent their death.


Subject(s)
COVID-19/genetics , COVID-19/virology , Cellular Senescence/genetics , Gene Expression Profiling , Neurons/pathology , Oxidative Stress/genetics , SARS-CoV-2/physiology , Caspase 3/metabolism , Cell Death , Cell Line , Cyclooxygenase 2/metabolism , Humans , Superoxide Dismutase/metabolism , Virus Replication/physiology
6.
Oxid Med Cell Longev ; 2021: 9919466, 2021.
Article in English | MEDLINE | ID: covidwho-1358940

ABSTRACT

Thrombus is considered to be the pathological source of morbidity and mortality of cardiovascular disease and thrombotic complications, while oxidative stress is regarded as an important factor in vascular endothelial injury and thrombus formation. Therefore, antioxidative stress and maintaining the normal function of vascular endothelial cells are greatly significant in regulating vascular tension and maintaining a nonthrombotic environment. Leonurine (LEO) is a unique alkaloid isolated from Leonurus japonicus Houtt (a traditional Chinese medicine (TCM)), which has shown a good effect on promoting blood circulation and removing blood stasis. In this study, we explored the protective effect and action mechanism of LEO on human umbilical vein endothelial cells (HUVECs) after damage by hydrogen peroxide (H2O2). The protective effects of LEO on H2O2-induced HUVECs were determined by measuring the cell viability, cell migration, tube formation, and oxidative biomarkers. The underlying mechanism of antioxidation of LEO was investigated by RT-qPCR and western blotting. Our results showed that LEO treatment promoted cell viability; remarkably downregulated the intracellular generation of reactive oxygen species (ROS), malondialdehyde (MDA) production, and lactate dehydrogenase (LDH); and upregulated the nitric oxide (NO) and superoxide dismutase (SOD) activity in H2O2-induced HUVECs. At the same time, LEO treatment significantly promoted the phosphorylation level of angiogenic protein PI3K, Akt, and eNOS and the expression level of survival factor Bcl2 and decreased the expression level of death factor Bax and caspase3. In conclusion, our findings suggested that LEO can ameliorate the oxidative stress damage and insufficient angiogenesis of HUVECs induced by H2O2 through activating the PI3K/Akt-eNOS signaling pathway.


Subject(s)
Gallic Acid/analogs & derivatives , Oxidative Stress/drug effects , Signal Transduction/drug effects , Cell Movement/drug effects , Cell Survival/drug effects , Gallic Acid/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Hydrogen Peroxide/pharmacology , Malondialdehyde/metabolism , Medicine, Chinese Traditional , Neovascularization, Physiologic/drug effects , Nitric Oxide Synthase Type III/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism
7.
BMC Complement Med Ther ; 21(1): 192, 2021 Jul 05.
Article in English | MEDLINE | ID: covidwho-1317123

ABSTRACT

BACKGROUND: Lippia javanica (lemon bush) is commonly used in the treatment of respiratory ailments, including asthma in southern African countries but there is no scientific evidence to support this claim. This study investigated the anti-inflammatory, antioxidant and anti-asthmatic effects of L. javanica using a rat model of asthma. METHODS: A 5% w/v L. javanica tea infusion was prepared and characterised by liquid chromatography-mass spectrometer (LC-MS). Animals were intraperitoneally sensitized with ovalbumin (OVA) and subsequently challenged intranasal with OVA on day 15 except the control group. Animals were grouped (n = 5/group) for treatment: unsensitised control, sensitised control, sensitised + prednisolone and sensitised + L. javanica at 50 mg/kg/day and 100 mg/kg/day - equivalent to 1 and 2 cups of tea per day, respectively. After 2 weeks of treatment, bronchoalveolar lavage fluid (BALF) was collected for total and differential white blood cell (WBC) count. Nitric oxide (NO), lipid peroxidation and antioxidants were also assessed in BALF. Ovalbumin specific IgE antibody and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-alpha were measured in serum. Lung and muscle tissues were histological examined. RESULTS: L. javanica was rich in phenolic compounds. OVA sensitisation resulted in development of allergic asthma in rats. L. javanica treatment resulted in a reduction in total WBC count as well as eosinophils, lymphocytes and neutrophils in BALF. L. javanica inhibited Th2-mediated immune response, which was evident by a decrease in serum IgE and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-α. L. javanica treatment also reduced malondialdehyde (MDA) and NO, and increased superoxide dismutase, glutathione and total antioxidant capacity. Histology showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and bronchiole smooth muscle thickening. CONCLUSION: L. javanica suppressed allergic airway inflammation by reducing Th2-mediated immune response and oxidative stress in OVA-sensitized rats which may be attributed to the presence of phenolic compound in the plant. This finding validates the traditional use of L. javanica in the treatment of respiratory disorders.


Subject(s)
Asthma/drug therapy , Lippia , Teas, Herbal , Animals , Antioxidants/metabolism , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Cytokines/blood , Disease Models, Animal , Eosinophils/metabolism , Glutathione/metabolism , Immunoglobulin E/blood , Leukocyte Count , Lung/pathology , Lymphocytes/metabolism , Malondialdehyde/metabolism , Neutrophils/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Rats, Wistar , Superoxide Dismutase/metabolism , Th2 Cells/drug effects
8.
BMC Complement Med Ther ; 21(1): 192, 2021 Jul 05.
Article in English | MEDLINE | ID: covidwho-1296592

ABSTRACT

BACKGROUND: Lippia javanica (lemon bush) is commonly used in the treatment of respiratory ailments, including asthma in southern African countries but there is no scientific evidence to support this claim. This study investigated the anti-inflammatory, antioxidant and anti-asthmatic effects of L. javanica using a rat model of asthma. METHODS: A 5% w/v L. javanica tea infusion was prepared and characterised by liquid chromatography-mass spectrometer (LC-MS). Animals were intraperitoneally sensitized with ovalbumin (OVA) and subsequently challenged intranasal with OVA on day 15 except the control group. Animals were grouped (n = 5/group) for treatment: unsensitised control, sensitised control, sensitised + prednisolone and sensitised + L. javanica at 50 mg/kg/day and 100 mg/kg/day - equivalent to 1 and 2 cups of tea per day, respectively. After 2 weeks of treatment, bronchoalveolar lavage fluid (BALF) was collected for total and differential white blood cell (WBC) count. Nitric oxide (NO), lipid peroxidation and antioxidants were also assessed in BALF. Ovalbumin specific IgE antibody and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-alpha were measured in serum. Lung and muscle tissues were histological examined. RESULTS: L. javanica was rich in phenolic compounds. OVA sensitisation resulted in development of allergic asthma in rats. L. javanica treatment resulted in a reduction in total WBC count as well as eosinophils, lymphocytes and neutrophils in BALF. L. javanica inhibited Th2-mediated immune response, which was evident by a decrease in serum IgE and inflammatory cytokines: IL-4, IL-5, IL-13 and TNF-α. L. javanica treatment also reduced malondialdehyde (MDA) and NO, and increased superoxide dismutase, glutathione and total antioxidant capacity. Histology showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and bronchiole smooth muscle thickening. CONCLUSION: L. javanica suppressed allergic airway inflammation by reducing Th2-mediated immune response and oxidative stress in OVA-sensitized rats which may be attributed to the presence of phenolic compound in the plant. This finding validates the traditional use of L. javanica in the treatment of respiratory disorders.


Subject(s)
Asthma/drug therapy , Lippia , Teas, Herbal , Animals , Antioxidants/metabolism , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Cytokines/blood , Disease Models, Animal , Eosinophils/metabolism , Glutathione/metabolism , Immunoglobulin E/blood , Leukocyte Count , Lung/pathology , Lymphocytes/metabolism , Malondialdehyde/metabolism , Neutrophils/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Rats, Wistar , Superoxide Dismutase/metabolism , Th2 Cells/drug effects
9.
Biomed Pharmacother ; 141: 111823, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1272313

ABSTRACT

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice.


Subject(s)
Ascorbic Acid/chemistry , Ascorbic Acid/therapeutic use , Magnesium Sulfate/chemistry , Magnesium Sulfate/therapeutic use , Niacinamide/chemistry , Niacinamide/therapeutic use , Pantothenic Acid/chemistry , Pantothenic Acid/therapeutic use , Pyridoxine/chemistry , Pyridoxine/therapeutic use , Riboflavin/chemistry , Riboflavin/therapeutic use , Sepsis/drug therapy , Sepsis/metabolism , Thiamine/chemistry , Thiamine/therapeutic use , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/therapeutic use , Ascorbic Acid/pharmacology , Dogs , Dose-Response Relationship, Drug , Drug Combinations , Drug Compounding , Female , Humans , Lipopolysaccharides/toxicity , Magnesium Sulfate/pharmacology , Male , Mice , Mice, Inbred BALB C , Niacinamide/pharmacology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Pantothenic Acid/pharmacology , Pyridoxine/pharmacology , Rats , Rats, Sprague-Dawley , Rats, Wistar , Riboflavin/pharmacology , Sepsis/pathology , Superoxide Dismutase/metabolism , Thiamine/pharmacology
10.
Eur Rev Med Pharmacol Sci ; 25(8): 3154-3161, 2021 04.
Article in English | MEDLINE | ID: covidwho-1227268

ABSTRACT

OBJECTIVE: While both first-line antioxidant enzymes and oxidation products have been considered as markers of periodontal disease, their assessment in the diagnosis of periodontal disease is more complicated. Some, such as superoxide dismutase (SOD, glutathione peroxidase (GPx) and reduced glutathione (GSH), have indicated significant differences between patients with chronic and aggressive periodontitis. PATIENTS AND METHODS: Participants (101) were divided into a control group of healthy individuals and, following diagnosis, patients with gingivitis, chronic periodontitis, and aggressive periodontitis. Compounds reflecting tissue destruction, inflammatory processes or antioxidant responses, such as sirtuins (SIRT-1, SIRT-2), metalloproteinases (MMP), SOD, GPx, GSH, and glutathione reductase (GR) were measured in saliva. RESULTS: SIRT-2 levels were significantly increased in all patients. In patients with gingivitis, MMP (p<0.05) and GPx (p<0.01) were significantly increased. In patients with chronic and aggressive periodontitis, SOD activities were increased (p<0.001) while GPx and GR were decreased (p<0.001). Relative activities of MMP were higher in patients with aggressive periodontitis. CONCLUSIONS: Measurements of SIRT-2 and SOD clearly showed increased levels of oxidative stress in cases of periodontitis with a subsequent inhibition of other antioxidant enzymes. Levels of GSH suggest reversibility of the conditions with appropriate intervention. With the assessment of the trends of these selected antioxidant markers, it is possible to determine the prognosis of the disease.


Subject(s)
Periodontitis/metabolism , Saliva/metabolism , Sirtuin 2/metabolism , Superoxide Dismutase/metabolism , Biomarkers/analysis , Biomarkers/metabolism , Humans , Periodontitis/diagnosis , Prognosis , Sirtuin 2/analysis , Superoxide Dismutase/analysis
11.
Autoimmunity ; 54(4): 213-224, 2021 06.
Article in English | MEDLINE | ID: covidwho-1201340

ABSTRACT

Currently, the novel coronavirus pneumonia has been widespread globally, and there is no specific medicine. In response to the emergency, we employed bioinformatics methods to investigate the virus's pathogenic mechanism, finding possible control methods. We speculated in previous studies that E protein was associated with viral infectivity. The present study adopted the domain search techniques to analyse the E protein. According to the results, the E protein could bind iron or haem. The iron and haem bound by the E protein came from the attacked haemoglobin and phagocytes. When E protein was attached to haem, it synthesised oxygen and water into superoxide anions, hydrogen peroxide and hydroxyl radicals. When the iron-bound E protein and the haem-bound E protein worked together, they converted superoxide anions and hydrogen peroxide into oxygen and water. These were the "ROS attack" and "ROS escape" of the virus. "ROS attack" damaged the tissues or cells exposed on the surface of the virus, and "ROS escape" decomposed the superoxide anion and hydrogen peroxide that attacked the virus. When NK cells were exposed to infected cells, viruses that had not shed from the infected cells' surface damaged them through "ROS attack". In addition, lymphocytes such as T cells and B cells, which could be close to the antigen of the virus surface, were also easily damaged or killed by the "ROS attack", generating a decrease in lymphocytes. When memory B cells were exposed to the virus's surface antigen, they were also damaged by "ROS attack", resulting in the patient's re-infection. The virus applied the "ROS escape" to decompose hydrogen peroxide released by phagocytes into oxygen and water. The surrounding cells were replenished with oxygen, and the patient was in a "happy hypoxia" state. When the phagocytes swallowed the virus, the E protein converted superoxide anions into oxygen and water. In this way, the virus parasitized in the vesicles of the phagocyte. While virus was in the lysosome, the E protein generated ROS to damage nearby hydrolases. In this way, the virus parasitized the lysosome. Excessive hydroxyl free radicals destroyed the membrane structure of the lysosome, causing the hydrolase release from lysosome, autophagy of phagocytic cells and subsequent cell death. As a result, the colonizing phagocytes of the virus was associated with asymptomatic infection or retest-positive. Briefly, the virus inhibited the immune system through "ROS escape", and damaged the immune system by "ROS attack". The destruction instigated a strong cytokine storm, leading to organ failure and complications.


Subject(s)
COVID-19/etiology , COVID-19/metabolism , Disease Susceptibility , Host-Pathogen Interactions , Immune System/immunology , Immune System/metabolism , Iron/metabolism , Reactive Oxygen Species/metabolism , SARS-CoV-2/physiology , Amino Acid Sequence , Catalysis , Computational Biology/methods , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Immune System/pathology , Models, Molecular , Protein Conformation , Structure-Activity Relationship , Superoxide Dismutase/metabolism , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/metabolism
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