scholarly journals Farmacocinética y farmacodinamia del dióxido de cloro

e-CUCBA ◽  
2021 ◽  
Vol 8 (16) ◽  
pp. 21-35
Author(s):  
Alberto Rubio-Casillas ◽  
◽  
Pablo Cambra-Madrid ◽  
Keyword(s):  
Antioxidant Enzymes ◽  
Hypochlorous Acid ◽  
Inflammatory Responses ◽  
Chemical Reactivity ◽  
Active Agent ◽  
Taurine Chloramine ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Low Concentrations ◽  
Functional Product ◽  
Gastric Secretions

Chlorine dioxide (ClO2) is widely used as a drinking water disinfectant in many countries. Due to its antibiotic and antiviral capacity, it has aroused interest as a potential therapeutic agent with respect to the COVID-19 disease, AIDS and Influenza. As a result of this debate in scientific and governmental settings, it was deemed highly timely to provide an up-to-date assessment of the pharmacokinetics and pharmacodynamics of ClO2. The main findings indicate that, due to its high chemical reactivity, ClO2 is rapidly reduced in oral and gastric secretions, producing chlorite (ClO2⁻), which becomes the active agent responsible for its systemic actions. ClO2 also showed potential to act as an oxidant or antioxidant depending on the concentration. Of particular therapeutic interest are the findings that, at low concentrations, ClO2⁻ can protect erythrocytes from oxidative stress while inhibiting excessive production of hypochlorous acid (HClO) mediated by myeloperoxidase (MPO), thus reversing the inflammatory responses and macrophage activation. Finally, taurine-chloramine represents the most relevant functional product formed under the influence of ClO2⁻, said molecule activates the erythroid nuclear factor 2 (Nrf2), (this transcription factor regulates the inducible expression of numerous genes for detoxifying and antioxidant enzymes) , increases the expression of heme-oxygenase (HO-1), protects cells from death caused by hydrogen peroxide (H2O2), improves the expression and activities of antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase, and contributes to the resolution of the inflammatory process.

Farmacocinética y farmacodinamia del dióxido de cloro

e-CUCBA ◽  
2021 ◽  
Vol 8 (16) ◽  
pp. 21-35
Author(s):  
Alberto Rubio-Casillas ◽  
◽  
Pablo Campra-Madrid ◽  
Keyword(s):  
Antioxidant Enzymes ◽  
Hypochlorous Acid ◽  
Inflammatory Responses ◽  
Chemical Reactivity ◽  
Active Agent ◽  
Taurine Chloramine ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Low Concentrations ◽  
Functional Product ◽  
Gastric Secretions

Chlorine dioxide (ClO2) is widely used as a drinking water disinfectant in many countries. Due to its antibiotic and antiviral capacity, it has aroused interest as a potential therapeutic agent with respect to the COVID-19 disease, AIDS and Influenza. As a result of this debate in scientific and governmental settings, it was deemed highly timely to provide an up-to-date assessment of the pharmacokinetics and pharmacodynamics of ClO2. The main findings indicate that, due to its high chemical reactivity, ClO2 is rapidly reduced in oral and gastric secretions, producing chlorite (ClO2⁻), which becomes the active agent responsible for its systemic actions. ClO2 also showed potential to act as an oxidant or antioxidant depending on the concentration. Of particular therapeutic interest are the findings that, at low concentrations, ClO2⁻ can protect erythrocytes from oxidative stress while inhibiting excessive production of hypochlorous acid (HClO) mediated by myeloperoxidase (MPO), thus reversing the inflammatory responses and macrophage activation. Finally, taurine-chloramine represents the most relevant functional product formed under the influence of ClO2⁻, said molecule activates the erythroid nuclear factor 2 (Nrf2), (this transcription factor regulates the inducible expression of numerous genes for detoxifying and antioxidant enzymes) , increases the expression of heme-oxygenase (HO-1), protects cells from death caused by hydrogen peroxide (H2O2), improves the expression and activities of antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase, and contributes to the resolution of the inflammatory process.

Immunomodulatory role of paliperidone in the poly(I:C) model of schizophrenia

2016 ◽  
Vol 33 (S1) ◽  
pp. s220-s221
Author(s):  
K. MacDowell ◽  
E. Munarriz-Cuezva ◽  
D. Martín-Hernández ◽  
A. Sayd ◽  
B. García-Bueno ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Inflammatory Responses ◽  
Poly I:C ◽  
Mrna Levels ◽  
Behavioral Test ◽  
Inflammatory Pathways ◽  
Anti Inflammatory ◽  
Cellular Markers ◽  
Endogenous Antioxidant

IntroductionAlterations on the innate inflammatory response may underlie the pathophysiology of psychiatric diseases, but the mechanisms implicated remain elusive. Current antipsychotics modulate pro/anti-inflammatory pathways, but the specific mechanisms involved remain elusive. One attractive possibility is the regulation of the intracellular signalling pathways of the innate immune receptors Toll-like 3 (TLR3), which triggers antiviral and inflammatory responses.AimsTo elucidate the regulatory role of paliperidone on maternal immune activation (MIA) induced alterations on TLR3 pathway and on the two emerging endogenous antiinflammatory/antioxidant mechanisms NRF2/antioxidant enzymes pathway and the cytokine milieu regulating M1/M2 polarization in microglia.MethodsPregnant mice were treated with the synthetic Toll-like Receptor 3 (TLR3) agonist Poly(I:C) in gestational day 9 and chronically treated with paliperidone (0,05 mg/kg i.p.) in adult offspring. Animals were sacrificed one day after treatment and behavioral test. Inflammation oxidative stress-related mediators were analysed at mRNA and protein level in prefrontal cortex samples. In addition, behavioral test t-maze was conducted.ResultsPaliperidone prevented TLR3 pathway activation and the subsequent MIA-induced neuroinflammatory response. Also, paliperidone induced an increment in the activity and protein expression of nuclear NRF2, as well as increased mRNA levels of the antioxidant enzymes HO1, SOD and catalase in the MIA model. Otherwise, paliperidone increases the antiinflammatory cytokines levels TGFβ and IL-10 in favour of a M2 microglia profile and increased the levels of the M2 cellular markers ArgI and FOLR2.ConclusionsThe modulation of neuroinflammation and enhancement of endogenous antioxidant/anti-inflammatory pathways by current and new antipsychotics could represent an interesting therapeutic strategy for the future.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Histamine receptors as drug target: Current and future therapeutics.

2019 ◽  
Vol 2 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Atteqa Jawad ◽  
Richa Kaushal ◽  
Muhammad Sohail ◽  
Amna Yaqoob
Keyword(s):  
Drug Target ◽  
Inflammatory Responses ◽  
Experimental Studies ◽  
Gastric Ulcers ◽  
Central Regulation ◽  
Inflammatory Reactions ◽  
Central Effects ◽  
Memory Modulation ◽  
Gastric Secretions

Histamine is a neurotransmitter responsible for central regulation of inflammatory reactions. Initial studies were done by Sir Henry Dale in 1993. Histamine acts on its four type of receptors. H1 and H2 are well-established with pharmacological status. H1 receptors are mainly linked with inflammatory responses and developed to mitigate the inflammatory symptoms. While H2 antagonists are established with their role in decreasing basal gastric secretions by decreasing the cyclic adenylyl mono phosphate (cAMP), thus used as therapy line for gastric ulcers. H3 being located centrally imparts its central effects in cognitive functions that are pain, sleep, and memory modulation of neurotransmitters release including, dopamine, acetylcholine, noradrenalin and serotonin. H4 is discovered recently during cloning of H3 and found on immune related cells as, mast cells, T cells and dendrites. Experimental studies are helping in development of more pharmacologically worth drugs that can increase the quality of life.

scholarly journals Micronutrients Selenomethionine and Selenocysteine Modulate the Redox Status of MCF-7 Breast Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 865 ◽  
Author(s):  
Daniel Gabriel Pons ◽  
Carmen Moran ◽  
Marina Alorda-Clara ◽  
Jordi Oliver ◽  
Pilar Roca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hydrogen Peroxide ◽  
Antioxidant Enzymes ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Redox Status ◽  
Hydrogen Peroxide Production ◽  
Low Concentrations ◽  
Mcf 7

Selenium is a micronutrient which is found in many foods, with redox status modulation activity. Our aim was to evaluate the effects of two chemical forms of selenoamino acids, Seleno-L-methionine and Seleno-L-cystine (a diselenide derived from selenocysteine), at different concentrations on cell viability, hydrogen peroxide production, antioxidant enzymes, UCP2 protein expression, as well as lipid and protein oxidative damage in MCF-7 breast cancer cells. Results showed that Seleno-L-methionine did not cause an increase in hydrogen peroxide production at relatively low concentrations, accompanied by a rise in the antioxidant enzymes catalase and MnSOD, and UCP2 protein expression levels. Furthermore, a decrease in protein and lipid oxidative damage was observed at 10 µM concentration. Otherwise, Seleno-L-cystine increased hydrogen peroxide production from relatively low concentrations (100 nM) to a large increase at high concentrations. Moreover, at 10 µM, Seleno-L-cystine decreased UCP2 and MnSOD protein expression. In conclusion, the chemical form of selenoamino acid and their incorporation to selenoproteins could affect the regulation of the breast cancer cell redox status. Taken together, the results obtained in this study imply that it is important to control the type of selenium-enriched nutrient consumption, taking into consideration their composition and concentration.

scholarly journals Basal anti-inflammatory responses in cultured endothelial cells exposed to two conjugated linoleic acids

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Carina Valenzuela ◽  
Elizabeth Miles ◽  
Philip Calder
Keyword(s):  
Inflammatory Responses ◽  
Adhesion Assay ◽  
Dependent Manner ◽  
Relative Expression ◽  
Inflammatory Pathways ◽  
Expression Of Genes ◽  
Low Concentrations ◽  
Genes Encoding ◽  
Anti Inflammatory ◽  
Pre Treatment

AbstractConjugated linoleic acid (CLA) isomers have been shown to possess anti-atherosclerotic properties, which may be related to the downregulation of inflammatory pathways. Whether low concentrations of CLAs are able to affect basal, unstimulated endothelial cell (EC) responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 and trans-10, cis-12) on basal inflammatory responses by ECs.EA.hy926 cells (HUVEC lineage) were cultured under standard conditions and exposed to CLAs (1 and 10 μM) for 48 hours. MTT assay was performed to determine cell viability; incorporation of FA was confirmed by gas chromatography; inflammatory mediators were assessed by multiplex immunoassay; the relative expression of genes encoding transcription factors and inflammatory cytokines was assessed through real-time PCR and static adhesion assay was used to evaluate monocyte attachment to the EC monolayer.CLAs were incorporated into ECs in a dose-dependent manner. Pre-treatment with CLA9,11 (1 uM) significantly reduced unstimulated, basal concentrations of MCP-1 (p < 0.05), and CLA10,12 at 10 uM had the same effect (p < 0.05). Both CLAs at 10 uM increased the relative expression of NFκβ (p < 0.01 and p < 0.05, respectively), while decreasing the relative expression of PPARα (p < 0.0001), COX-2 (p < 0.0001) and IL-6 (p < 0.0001). In contrast, no effect was observed in the adhesion assay for either CLA.These results suggest that both CLAs at a low concentration have a neutral or modest anti-inflammatory effect in basal conditions, which may influence endothelial function and risk of vascular disease. Interestingly, at these low CLA concentrations some pro-inflammatory genes are upregulated while others are down regulated. This suggests complex effects of CLAs on inflammatory pathways.

scholarly journals Physiochemical Studies of Sodium Chloride on Mungbean (Vigna radiataL. Wilczek) and Its Possible Recovery with Spermine and Gibberellic Acid

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Srijita Ghosh ◽  
Sanglap Mitra ◽  
Atreyee Paul
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Gibberellic Acid ◽  
Chlorophyll Content ◽  
Biomass Production ◽  
Oxidative Stress Marker ◽  
Antioxidant Enzyme Activities ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Low Concentrations

The physiological and biochemical responses to increasing NaCl concentrations, along with low concentrations of gibberellic acid or spermine, either alone or in their combination, were studied in mungbean seedlings. In the test seedlings, the root-shoot elongation, biomass production, and the chlorophyll content were significantly decreased with increasing NaCl concentrations. Salt toxicity severely affected activities of different antioxidant enzymes and oxidative stress markers. Activities of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) increased significantly over water control. Similarly, oxidative stress markers such as proline, malondialdehyde (MDA), and hydrogen peroxide (H2O2) contents also increased as a result of progressive increase in salt stress. Combined application of NaCl along with low concentrations of either gibberellic acid (5 µM) or spermine (50 µM) in the test seedlings showed significant alterations, that is, drastic increase in seedling elongation, increased biomass production, increased chlorophyll content, and significant lowering in all the antioxidant enzyme activities as well as oxidative stress marker contents in comparison to salt treated test seedlings, leading to better growth and metabolism. Our study shows that low concentrations of either gibberellic acid or spermine will be able to overcome the toxic effects of NaCl stress in mungbean seedlings.

scholarly journals Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease

2009 ◽  
Vol 16 (5) ◽  
pp. 660-666 ◽  
Author(s):  
Monisha Dhiman ◽  
Jose Guillermo Estrada-Franco ◽  
Jasmine M. Pando ◽  
Francisco J. Ramirez-Aguilar ◽  
Heidi Spratt ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Nitrosative Stress ◽  
Hypochlorous Acid ◽  
Inflammatory Responses ◽  
Neutrophil Activation ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Myeloperoxidase Activity ◽  
Protein Nitration ◽  
Specific Antibodies

ABSTRACT In this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with Chagas' disease. We used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and STAT-PAK immunochromatography) to screen human serum samples (n = 1,481) originating from Chiapas, Mexico, for Trypanosoma cruzi-specific antibodies. We identified 121 subjects who were seropositive for T. cruzi-specific antibodies, a finding indicative of an 8.5% seroprevalence in the rural population from Chiapas. Seropositive and seronegative subjects were examined for plasma levels of biomarkers of inflammation, i.e., myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and xanthine oxidase (XOD), as well as for oxidative (advanced oxidation protein products [AOPPs]) and nitrosative (3-nitrotyrosine [3NT]) biomarkers. The seropositive subjects exhibited a significant increase in MPO activity and protein level, the indicator of neutrophil activation. Subsequently, a corresponding increase in AOPP contents, formed by MPO-dependent hypochlorous acid and chloramine formation, was noted in seropositive subjects. The plasma level of 3NT was significantly increased in seropositive subjects, yet we observed no change in XOD activity (O2 − source) and nitrate/nitrite contents (denotes iNOS activation and NO production), which implied that direct peroxynitrite formation does not contribute to increased nitrosative damage in chagasic subjects. Instead, a positive correlation between increased MPO activity and protein 3NT formation was observed, which suggested to us that MPO-dependent formation of nitrylchloride that occurs in the presence of physiological NO and O2 − concentrations contributes to protein nitration. Overall, our data demonstrate that T. cruzi-induced neutrophil activation is pathological and contributes to MPO-mediated collateral protein oxidative and nitrosative damage in human patients with Chagas' disease. Therapies capable of suppressing MPO activity may be useful in controlling the inflammation and oxidative/nitrosative pathology in chagasic cardiomyopathy.

3,3′,5,5′-Tetramethylbenzidine in hypochlorous acid and taurine chloramine scavenging assays: interference of dimethyl sulfoxide and other vehicles

2013 ◽  
Vol 437 (2) ◽  
pp. 130-132 ◽  
Author(s):  
Luciana M. Kabeya ◽  
Micássio F. Andrade ◽  
Fabiana Piatesi ◽  
Ana Elisa C.S. Azzolini ◽  
Ana Cristina M. Polizello ◽  
...  
Keyword(s):  
Dimethyl Sulfoxide ◽  
Hypochlorous Acid ◽  
Taurine Chloramine

scholarly journals TGF-β regulates Nox4, MnSOD and catalase expression, and IL-6 release in airway smooth muscle cells

2011 ◽  
Vol 300 (2) ◽  
pp. L295-L304 ◽  
Author(s):  
Charalambos Michaeloudes ◽  
Maria B. Sukkar ◽  
Nadia M. Khorasani ◽  
Pankaj K. Bhavsar ◽  
Kian Fan Chung
Keyword(s):  
Smooth Muscle ◽  
Antioxidant Enzymes ◽  
Airway Smooth Muscle ◽  
Manganese Superoxide Dismutase ◽  
Redox Regulation ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Chronic Obstructive ◽  
Airway Smooth Muscle Cells ◽  
Nadph Oxidase 4

Reactive oxygen species (ROS) are generated as a result of normal cellular metabolism, mainly through the mitochondria and peroxisomes, but their release is enhanced by the activation of oxidant enzymes such as NADPH oxidases or downregulation of endogenous antioxidant enzymes such as manganese-superoxide dismutase (MnSOD) and catalase. Transforming growth factor-β (TGF-β), found to be overexpressed in airway smooth muscle (ASM) from asthmatic and chronic obstructive pulmonary disease patients, may be a pivotal regulator of abnormal ASM cell (ASMC) function in these diseases. An important effect of TGF-β on ASMC inflammatory responses is the induction of IL-6 release. TGF-β also triggers intracellular ROS release in ASMCs by upregulation of NADPH oxidase 4 (Nox4). However, the effect of TGF-β on the expression of key antioxidant enzymes and subsequently on oxidant/antioxidant balance is unknown. Moreover, the role of redox-dependent pathways in the mediation of the proinflammatory effects of TGF-β in ASMCs is unclear. In this study, we show that TGF-β induced the expression of Nox4 while at the same time inhibiting the expression of MnSOD and catalase. This change in oxidant/antioxidant enzymes was accompanied by elevated ROS levels and IL-6 release. Further studies revealed a role for Smad3 and phosphatidyl-inositol kinase-mediated pathways in the induction of oxidant/antioxidant imbalance and IL-6 release. The changes in oxidant/antioxidant enzymes and IL-6 release were reversed by the antioxidants N-acetyl-cysteine (NAC) and ebselen through inhibition of Smad3 phosphorylation, indicating redox-dependent activation of Smad3 by TGF-β. Moreover, these findings suggest a potential role for NAC in preventing TGF-β-mediated pro-oxidant and proinflammatory responses in ASMCs. Knockdown of Nox4 using small interfering RNA partially prevented the inhibition of MnSOD but had no effect on catalase and IL-6 expression. These findings provide novel insights into redox regulation of ASM function by TGF-β.

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