Acute respiratory distress syndrome (ARDS) remains to be a paramount healthcare issue, frequently resulting in respiratory failure and death.Recently, the rapidly expanding knowledge about the pathophysiology of novel severe acute respiratory syndrome (nSARS-CoV-2) infection provides a significant insight regarding the implication of cytokines storm, which mainly causes an acute lung injury (ALI) in COVID-19 patients and directs the disease severity.As hypoxemia worsens, ALI can progress into ARDS leading to a high mortality rate.Despite advances in clinical care, the lungs of a subset of ARDS survivors show persistent fibrotic changes triggered by an imbalance between higher reactive oxidative species and lower anti-oxidative substrates.Clinical evidence have shown the pneumoprotective effects of quercetin in certain pulmonary conditions.Albeit many studies evaluating quercetin's anti-inflammatory action on bacterial lipopolysaccharide-induced models have been done, anti-inflammatory studies using viral-induced models or its surrogate are still lacking.In this review, the authors discuss the possible molecular mechanism of quercetin in targeting specific pathways in lung injury and its sequelae, including pulmonary fibrosis that is induced both by infectious and pneumotoxic agents.
The viscosity of a fluid is a measure of its resistance. It is the thickness and stickiness of blood, and a direct measure of the resistance of blood to flow through the vessels. Various factors in the blood have direct or indirect impact on blood viscosity. These hemorheological factors play an important role in the pathogenesis of many diseases. Glucose is one such factor, which, when increased in the blood, causes resistance in the blood flow.The present study is aimed to assess the changes in blood viscosity associated with hyperglycemia in rodents.Diabetic patients were grouped, depending on the duration of their diabetic status assessed by their increased HbA1c. Similarly rodents were subjected to acute or chronic hyperglycemic conditions in various experiments. In vivo, perfusion study was performed using micro probe in diabetic mice. Flow cytometry was used to assess the expression of VCAM-1 on endothelial surface.An approximate 40% increase in blood viscosity is observed in individual who were diabetic for the past 15 years than those who were diagnosed just one year back. Similarly such increase in blood viscosity was evident in different experiments of rodents. Our in vivo perfusion study did not showed conclusive finding however long term hyperglycemia can have deleterious effect on flow rate. Vascular pathology which was evident from the data of flow cytometry, where increase in VCAM-1 expression on the endothelial surface was observed in response to glucose and in diabetic mice.Hyperglycemia implicates the blood viscosity which in turn can have tedious effect on metabolic syndromes thus causing the serious effect in the tissue perfusion of an organs.
Quercetin (QUE) is a primary polyphenol in the flavonoid family. It is categorized as one of the six subclasses of flavonoid compounds. As an abundant form of flavonoid molecules, quercetins are ubiquitously distributed in various dietary plants, including apples, berries, onions, bananas, tomatoes, and grapes. Furthermore, it is affordably marketed in the form of dietary supplement tablets. QUE is relatively lipophilic with low solubility in the water. Withal, QUE glucoside is more water soluble than the aglycone, and its absorption is limited to sodium-dependent glucose transporter-1 (SGLT-1); however, glucose transporter-2 (GLUT-2)-dependent absorption is also a significant contributor. Following absorption, QUE undergoes extensive metabolism in the liver, generating numerous metabolites. Data on the bioavailability of QUE differ substantially depending on the methods used for measuring QUE level. Pharmacokinetic interactions of QUE and its metabolites on cytochrome P450 enzymes have been studied extensively, but the results among the studies were inconsistent, such as weak inhibition toward CYP3A4 and no inhibition of CYP2D6 activity. Additionally, inhibition affects ATP- (adenosine triphosphate) binding cassette (ABC). Based on the pharmacokinetics profile, QUE has variable bioavailability based on the polymorphism of intestinal enzymes and transporters.
Objective: The present study was designed to evaluate the effect a commonly prescribed Non Steroidal Anti Inflammatory Drug (NSAID) i. e. aspirin on brush border membrane in terms of changes in the intestinal transport level of glucose which is monosaccharide with absolute requirement in the body and hence its absorption is directly proportional on the morphology of the intestinal mucosa. Method: Albino rats (Rattus Norvegicus) were divided into two different groups, Group Ⅰ(Control), Group Ⅱ (aspirin-treated, 50 mg aspirin/kg of body weight). The treatment was continued for 28 days. On the 29th day after overnight fasting, intestine was removed from animals of both groups. Changes in transport of glucose-D in intestine were studied. Result: The results indicated a significant decrease in the transport of glucose-D in aspirin treated group as compared to the control group. Conclusion: Cautious use of NSAID is recommended in commonly observed symptom such as headache and to those patients who are given as a prophylaxis for thrombosis.
Abstract BackgroundNickel, in the form of various alloys and compounds, has been in widespread commercial use for over 100 years. Several million workers worldwide are exposed to airborne fumes, dust, and mist containing nickel and its compounds. Further, exposures by inhalation, ingestion, or skin contact occur in nickel-producing industries, like mining, milling, melting, and refining, and in nickel-using industries, like electroplating, welding, and grinding. Insoluble nickel is the predominant exposure in nickel-producing industries, whereas soluble nickel is the predominant exposure in nickel-using industries like the ceramics industry. This study was designed to extrapolate the levels of serum nickel, antioxidant compounds, and stress markers and correlate them with lung function status in craft workers in the ceramics industryMethods The study included 50 fiber craft workers from the ceramics industry who met the inclusion criteria. The control group consisted of subjects from the general population with no disease. Blood samples from the workers were collected by a phlebotomist. The levels of nickel and biological antioxidants, i.e. serum glutathione (GSH) and stress marker malondialdehye (MDA), were determined. Estimation of oxidants and haptoglobin (Hp) levels were assessed. The level of nickel was measured by atomic absorption spectrophotometry. A spirometer was used to measure lung functions. The calculated levels of these parameters were compared with those in the control subjects.ResultAn overall increase in nickel and MDA levels and a decrease in GSH level were observed. When these workers were classified into groups, it was observed that prolonged employment in the ceramics industry was associated with an increased nickel concentration in the serum, which in turn increased oxidative stress biomarkers and thus decreased the antioxidant levels to the lower limit. The decrease in GSH level compromises lung function. Our findings of an increase the Hp level is noteworthy, as it increased by 89% in the group with over 10 years of service in the industry compared with the group working for less than 5 years. ConclusionDaily exposure to nickel for prolonged periods could result in fatal respiratory disease. Precautionary measures should be made mandatory in all industries.
Introduction: CD38 is a multifunctional enzyme with a potent Ca2+ mobilizing effect, cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP). Here, we aimed to demonstrate the role of CD38 in platelets via protein kinase C (PKC)-mediated internalization and activation. Methods: Mouse platelets were used in this study. Thrombin, an agonist of platelet function, provoked a prompt and long-lasting increase in intracellular Ca2+ concentration ([Ca2+]i), resulting from an interplay of multifold Ca2+ mobilizing messengers.The signaling pathway was delineated using different inhibitors and techniques such as platelet aggregation assay, intracellular calcium measurements, immunoprecipitation, immunoblotting, and flow cytometry. Results: We observed a sequential formation of cADPR and NAADP through CD38 activation by PKC of non-muscle myosin heavy chain IIA (MHCIIA), resulting in phospholipase C (PLC) activation in the thrombin-stimulated platelets. These findings reveal that PKC is fundamental in activating CD38 and elicits a physiological response in the murine platelets. Conclusion: PKC is involved in many signaling pathways. Specifically, PKC is involved in the internalization of CD38 via MHCIIA in CD38+/+ wild-type (WT) and CD38-/- knockout mice (KO). CD38 generates calcium-mobilizing agents that act on specific receptors of the calcium stores. Calcium triggered platelet aggregation while serving as a secondary messenger.
Hydrogen Peroxide (HP) is one of the Reactive Oxygen Species (ROS) causing cellular injury. The present study is aimed to assess the level of HP, catalase, total glutathione (T-GSH) in chronic smokers and compare these with acute smoker, passive smokers and non-smokers. In the peripheral blood of chronic smoker, acute smoker, passive smokers and control subjects, oxidative stress was measured in terms of HP present in the serum; antioxidant status was measured by blood T-GSH and catalase activity. Adverse effects of HP is measured in term of osmotic fragility of RBC. Increase amount of HP in serum of smoker was observed, whereas two fold increase of the HP was detected in the serum of acute smoker and moderate amount was detected in passive smoker as compare to non-smoker. Variability in the measurement of catalase and T-GSH were also significantly evident in the groups. Increase concentration of HP in acute smoker suggested that ROS produced in smoking not only have their adverse effects in the lungs but they can cross the alveolar epithelium. Osmotic fragility test indicated the increase in fragility of RBC membrane of smoker when they are subjected to high concentration of HP in vitro.
Abstract The full text of this preprint has been withdrawn, as it was submitted in error. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.
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