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SARS-CoV-2 infection affects and modulates serum as well as hematological parameters. However, whether it modifies these parameters in the existing disease conditions, which help in the erection of specific treatments for the disease, is under investigation. Here, we aimed to determine whether serum and hematological parameters alteration in various diseases, diabetes mellitus (DM), hypertension (HTN), ischemic heart disease (IHD) and myocardial infarction (MI) conditions correlate and signal SARS-CoV-2 infection, which could be used as a rapid diagnosis tool for SARS-CoV-2 infection in disease conditions. To assess the projected goals, we collected blood samples of 1,113 male and female patients with solo and multiple disease conditions of DM/HTN/IHD/MI with severe COVID-19, followed by biochemical analysis, including COVID-19 virus detection by RT-qPCR. Furthermore, blood was collected from age-matched disease and healthy individuals 502 and 660 and considered as negative control. In our results, we examined higher levels of serum parameters, including D-dimer, ferritin, hs-CRP, and LDH, as well as hematological parameters, including TLC in sole and multiple diseases (DM/HTN/IHD/MI) conditions compared to the control subjects. Besides, the hematological parameters, including Hb, RBC, and platelet levels, decreased in the patients. In addition, we found declined levels of leukocyte count (%), lymphocyte (%), monocyte (%), and eosinophil (%), and elevated level of neutrophil levels (%) in all the disease patients infected with SARS-CoV-2. Besides, NLR and NMR ratios were also statistically significantly (p < 0.05) high in the patients with solo and multiple disease conditions of DM/HTN/IHD/MI infected with the SARS-CoV-2 virus. In conclusion, rapid alteration of sera and hematological parameters are associated with SARS-CoV-2 infections, which could help signal COVID-19 in respective disease patients. Moreover, our results may help to improve the clinical management for the rapid diagnosis of COVID-19 concurrent with respective diseases.
ABSTRACT
Antibiotics, as a class of environmental pollutants, pose a significant challenge due to their persistent nature and resistance to easy degradation. This study delves into modeling and optimizing conventional Fenton degradation of antibiotic sulfamethoxazole (SMX) and total organic carbon (TOC) under varying levels of H2O2, Fe2+ concentration, pH, and temperature using statistical and artificial intelligence techniques including Multiple Regression Analysis (MRA), Support Vector Regression (SVR) and Artificial Neural Network (ANN). In statistical metrics, the ANN model demonstrated superior predictive accuracy compared to its counterparts, with lowest RMSE values of 0.986 and 1.173 for SMX and TOC removal, respectively. Sensitivity showcased H2O2/Fe2+ ratio, time and pH as pivotal for SMX degradation, while in simultaneous SMX and TOC reduction, fine tuning the time, pH, and temperature was essential. Leveraging a Hybrid Genetic Algorithm-Desirability Optimization approach, the trained ANN model revealed an optimal desirability of 0.941 out of 1000 solutions which yielded a 91.18% SMX degradation and 87.90% TOC removal under following specific conditions: treatment time of 48.5 min, Fe2+: 7.05 mg L-1, H2O2: 128.82 mg L-1, pH: 5.1, initial SMX: 97.6 mg L-1, and a temperature: 29.8 °C. LC/MS analysis reveals multiple intermediates with higher m/z (242, 270 and 288) and lower m/z (98, 108, 156 and 173) values identified, however no aliphatic hydrocarbon was isolated, because of the low mineralization performance of Fenton process. Furthermore, some inorganic fragments like NH4+ and NO3- were also determined in solution. This comprehensive research enriches AI modeling for intricate Fenton-based contaminant degradation, advancing sustainable antibiotic removal strategies.
Subject(s)
Anti-Bacterial Agents , Artificial Intelligence , Hydrogen Peroxide , Iron , Neural Networks, Computer , Sulfamethoxazole , Sulfamethoxazole/chemistry , Hydrogen Peroxide/chemistry , Anti-Bacterial Agents/chemistry , Iron/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Hydrogen-Ion Concentration , TemperatureABSTRACT
Endothelial dysfunction (ED) is a significant risk factor of blood vessel related diseases of diabetes and this study evaluate the effect of adding Momordica charantia (Mc) to glibenclamide (GLB) on ED markers in diabetic rats. Streptozotocin (STZ-40mg/kg b. w.) induced diabetic rats were randomly put into 3 groups with 10 rats/group; diabetic control [DC] group, glibenclamide treated group (GLB -2.5mg/kg) and GLB-Mc treated group (2.5mg/kg + 400mg/kg). Serum glucose was measured weekly for eight weeks whereas insulin, sVCAM-1, vWF-Ag and interleukin-6 [IL-6] were measured at week 0 and week 8. Luciferase assay was performed to determine luminescence. At week 8, GLB and GLB-Mc groups revealed improvements in blood glucose and insulin concentrations (P≤0.05) when compared to corresponding baseline values with GLB-Mc group showing slightly greater improvements. GLB-M c group also revealed improvement (P≤0.05) in vWF-Ag, sVCAM-1 and IL-6 concentrations but was non-significant in GLB group when compared to corresponding baseline values. Comparison between GLB and GLB-Mc group showed significantly high concentration of sVCAM-1 in GLB group (P≤0.05) due to its minimal effect on TGR5 activation. We conclude that adding M. charantia to GLB may be a useful choice for modulating diabetes induced ED due to its stimulatory effect on TGR5 receptors.
Subject(s)
Diabetes Mellitus, Experimental , Momordica charantia , Rats , Animals , Glyburide/pharmacology , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/drug therapy , Interleukin-6 , von Willebrand Factor , Plant Extracts/pharmacology , Blood Glucose , Insulin , Hypoglycemic Agents/pharmacologyABSTRACT
Photocatalytic degradation of dyes has been the subject of extensive study due to its low cost, eco-friendly operation, and absence of secondary pollutants. Copper oxide/graphene oxide (CuO/GO) nanocomposites are emerging as a new class of fascinating materials due to their low cost, nontoxicity, and distinctive properties such as a narrow band gap and good sunlight absorbency. In this study, copper oxide (CuO), graphene oxide (GO), and CuO/GO were synthesized successfully. X-ray diffractometer (XRD) and Fourier transform infrared (FTIR) spectroscopy confirm the oxidation and production of GO from the graphene of lead pencil. According to the morphological analysis of nanocomposites, CuO nanoparticles of sizes ≤20 nm on the GO sheets were evenly adorned and distributed. Nanocomposites of different CuO:GO ratios (1:1 up to 5:1) were applied for the photocatalytic degradation of methyl red (MR). CuO:GO(1:1) nanocomposites achieved 84% MR dye removal, while CuO:GO(5:1) nanocomposites achieved the highest value (95.48%). The thermodynamic parameters of the reaction for CuO:GO(5:1) were evaluated using the Van't Hoff equation and the activation energy was found to be 44.186 kJ/mol. The reusability test of the nanocomposites showed high stability even after seven cycles. CuO/GO catalysts can be used in the photodegradation of organic pollutants in wastewater at room temperature due to their excellent properties, simple synthesis process, and low cost.
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Clopidogrel, an antiplatelet drug, is frequently prescribed to patients diagnosed with ischemic diseases such as those suffering from acute coronary syndromes or ischemic stroke. Despite the drug being effective in majority of the patients, some still experience ischemic events early in the treatment which might be due to poor platelet inhibition. This study aims to investigate the association of cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms, haplotypes as well as a wide range of clinical and demographic variables with platelet aggregation phenotypes to clopidogrel in a Pakistani cohort. The study comprised of a total of 120 patients diagnosed with cardiovascular diseases and were treated with clopidogrel. Antiplatelet response to clopidogrel was monitored by Helena AggRAM (HL-2-1785P) and patients with maximal platelet aggregation more than 50% were categorized as low responders and those with less than 50% as high responders. Our results show that 56.6% of patients were homozygous for the CYP2C19 wild-type allele, 38.3% of patients possessed one copy of the CYP2C19*2 allele and 5% of patients possessed both CYP2C19*2 alleles. No CYP2C19*3 allele was found in our patient cohort. There was no statistically significant difference between the high and low responder groups to clopidogrel in terms of extensive, intermediate and poor metabolizer genotypes. However, haplotype (H1), leukocyte count, random blood glucose, and history of diabetes mellitus was associated with the antiplatelet response to clopidogrel. The prevalence of clopidogrel resistance in our population was in line with that reported for other regional and global populations.
Subject(s)
Platelet Aggregation Inhibitors , Ticlopidine , Clopidogrel/therapeutic use , Cytochrome P-450 CYP2C19/genetics , Genotype , Haplotypes , Humans , Ischemia/drug therapy , Pakistan , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Ticlopidine/adverse effects , Treatment OutcomeABSTRACT
Interindividual differences in cytochrome P450 (CYP) 2C19 activity may result in variations in the therapeutic response to drugs metabolized by this enzyme. Differences at gene level may translate into protein level with consequent impairment of the enzyme activity. As a result patients with such genetic differences might experience undesirable effects or no effect at all. The aim of the present study was to find out the prevalence of allelic and genotype frequencies of low activity variants of CYP2C19 genes in healthy individuals from six distinct ethnicities of Pakistan. Blood sample was taken from healthy volunteers following informed consent. Isolation of the DNA was followed by the PCR amplification and restriction fragment length polymorphism. Selected samples were sequenced by Sanger sequencing. The frequency of major alleles was 84.93% for CYP2C19*2 and 91.85% for CYP2C19*3, while minor allele was present at 15.06% for CYP2C19*2 and 8.14% for CYP2C19*3. For CYP2C19*2, the frequency of *1*1 genotype was 75.80%, *1*2 was 18.27%, and *2*2 was 5.92% whereas for CYP2C19*3, The frequency of *1*1 genotype was 84.19%, *1*3 was 15.30%, and *3*3 was 0.49% in the Pakistani population. A substantial variation in genotype and allelic frequencies was observed in various ethnicities. Our study demonstrates that a significant Pakistani population has at least one minor allele, which indicates a large number of patients potentially being affected by these variations. Especially, a significant genotype frequency of PM suggests implication for the treatment response and severity/frequency of adverse effects in patients receiving drugs metabolized by CYP2C19.
Subject(s)
Cytochrome P-450 CYP2C19/genetics , Ethnicity , Polymorphism, Genetic/genetics , Asian People/genetics , Asian People/statistics & numerical data , Cytochrome P-450 CYP2C19/chemistry , Ethnicity/genetics , Ethnicity/statistics & numerical data , Genotype , Humans , Pakistan/epidemiology , PharmacogeneticsABSTRACT
After Alzheimer's disease, Parkinson's disease (PD) has taken second place in becoming one of the most commonly occurring neurological diseases being responsible for a number of disabling motor symptoms ranging from bradykinesia, akinesia, tremors to rigidity, that mostly targets the elderly population and severely disrupts their quality of life. The true underlying pathology of PD yet remains a mystery, however, recent advances in the field have pointed towards the production of α-synuclein aggregates, oxidative stress, and an imbalance between levels of acetylcholine and dopamine neurotransmitters in the brain that have been shown to result in loss of coordinated movement. Current treatments of PD include the gold standard dopamine precursor L-dopa, dopamine agonists pergolide and bromocriptine, catechol-o-methyl transferases inhibitors, entacapone and tolcapone and monoamine oxidase inhibitors such as Selegine and Rasagiline amongst several other drugs. While these drugs are successful in treating motor symptoms of the disease, they do so with a plethora of side effects that are especially debilitating to the elderly. In the recent years, a considerable amount of attention has been shifted towards phytocompounds such as flavonoids and green tea catechins due to promising experimental results. In this review, we have compiled phytocompounds that have shown potent activity against some of the most important targets for antiparkinsonian therapy. These compounds have exhibited activities that transcend the limits of simply attenuating mitochondrial oxidative stress and have opened doors to the discovery of novel lead compounds for newer, efficacious antiparkinsonian therapies with wider therapeutic windows.
Subject(s)
Antiparkinson Agents/therapeutic use , Biological Products/therapeutic use , Dopamine Agonists/therapeutic use , Parkinson Disease/drug therapy , Plant Extracts/therapeutic use , Animals , Antiparkinson Agents/isolation & purification , Antiparkinson Agents/pharmacology , Biological Products/isolation & purification , Biological Products/pharmacology , Brain/drug effects , Brain/metabolism , Brain/pathology , Dopamine Agonists/isolation & purification , Dopamine Agonists/pharmacology , Humans , Levodopa/pharmacology , Levodopa/therapeutic use , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/therapeutic use , Parkinson Disease/metabolism , Parkinson Disease/pathology , Plant Extracts/isolation & purification , Plant Extracts/pharmacokineticsABSTRACT
This study explores the boosted regression trees (BRT), artificial neural network (ANN) and response surface methodology (RSM) to model and optimize the operational variables for the simulation of the Photolytic degradation of Sulfamethoxazole (SMX) and concurrent total organic carbon (TOC) removal, based on the experimental data set. Four candidate variables involving initial pH (2-11), initial SMX concentration (50-200 mg L-1), temperature (15-45 °C) and time (6-120 min) were considered for simultaneous optimization of SMX and TOC degradation. The result revealed that all the three models are statistically considerable as the values of R, R2, adj-R2 are >0.85, thus be deemed to work well in data fitting, prediction, and optimization, nevertheless, the values of R, R2, adj-R2, RMSE, MAE and AAD are far better for ANN and BRT than RSM method. The â¼100% SMX degradation conditions were found to be as follows: treatment time: 25 min, pH: 2.0, temperature: 35 °C and SMX concentration: 50 mg L-1, while the maximum possible removal of TOC under the given conditions was â¼25%. The percentage contribution (PC) of each variable was deduced by ANOVA analysis of proposed quadratic models which indicated that time and pH are important factors than temperature and SMX concentration. The photolytic intermediates and inorganic ions of SMX, were identified and a potential route of transformation was also proposed.
Subject(s)
Neural Networks, Computer , Sulfamethoxazole , Computer Simulation , Photolysis , TemperatureABSTRACT
Mental health is the most neglected health sector in Pakistan, and the majority of citizens have limited or no access to primary and secondary psychiatric services. The incidence of schizophrenia (SCZ) has increased at an alarming rate in Pakistan, relative to that of other psychiatric disorders. While numerous studies have investigated SCZ, few have addressed the issue about the Pakistani population. In the present review, the researchers discuss current data integral to the prevalence, pathophysiology, and molecular genetics of SCZ; treatment approaches to the disease; and patient responses to drugs prescribed for SCZ in Pakistan. Most Pakistani patients exhibit poor responses to antipsychotic drugs. Based on our review, the researchers hypothesize that genetic dissimilarities between Pakistani and Western populations contribute to such poor responses. Consequently, an understanding of such genetic differences and the provision of personalized treatment may simultaneously aid in improving SCZ treatment in Pakistan.
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Many studies have proposed an important role of viruses in the pathogenesis of oral cancer. The present study aimed to find out the prevalence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human papillomavirus (HPV) among patients with oral squamous cell carcinoma (OSCC) in a Pakistani cohort. We investigated tissue samples obtained from 58 patients with OSCC using the polymerase chain reaction assay. No sample was positive for HPV. EBV was identified in 15 patients (25.86%), and CMV in three patients (5.17%). Coinfection with one or more viruses was detected in two cases and was coinfection with EBV and CMV. These results suggest a low prevalence of these viruses in OSCC patients in the Pakistani population compared to most other countries where the prevalence of these viruses has been reported in the past. Nevertheless, further studies are necessary to determine the potential role of EBV and the possible importance of CMV as an infection cofactor in oral cancer.
ABSTRACT
This study examined the photo-assisted electrochemical degradation and mineralization of the antibiotic contaminant sulfamethoxazole (SMX). All the experiments were perform using a flow electrolytic cell, in which the influence of the current density (10-60 mA cm-2) and sodium chloride (0.02-0.10 mol L-1) in the supporting electrolyte composition was analyzed. The results showed that the total SMX and 50% TOC removal was achieved in the current density range used. As expected, the degradation kinetics presented a pseudo first order behavior and the rate constant increased from 0.05 min-1 to 0.50 min-1 as the current density raised from 10 to 60 mA cm-1. In addition, the values of the electrical energy per order (EEO) increased from 0.67 to 1.06 kW/hm-3 order-1 as the current density increased from 10 to 60 mAcm-2 and drop from 8.82 to 0.57 kW/hm-3 order-1 at supporting electrolyte concentration of 0.02-0.1 mol L-1. The reaction intermediates identified by liquid chromatography-mass spectrometry allowed proposing a mechanism for the degradation. The use of photo assistance in the electrochemical process involved simultaneous reactions, for example, aromatic ring substitutions and hydroxylation. These reactions led to aromatic rings opening that generated simpler organic molecules, making possible the mineralization of the SMX molecule. Probable degradation pathways were proposed and discussed. Comparison of the efficiencies of the photocatalytic, electrochemical (EC) and photo-assisted electrochemical (PAEC) techniques revealed that the combined process showed a synergism for TOC removal.
Subject(s)
Anti-Bacterial Agents , Sulfamethoxazole , Water Purification , Electrodes , Electrolysis , Oxidation-Reduction , TitaniumABSTRACT
BACKGROUND: The present study was designed to determine the effects of cyclooxygenase-2 (COX-2) inhibitor-nimesulide on platelet activating factor (PAF) and arachidonic acid (AA)-induced platelet aggregation during myocardial infarction (Ml) and ischaemia in rabbits. METHODS: Rabbits were divided into three groups; group I served as control and contains normal rabbits that received saline, group II rabbits received saline before induction of Ml, and group Ill rabbits received nimesulide (25 mg/kg) before Ml induction. Myocardial infarction was induced by isoproterenol (ISP) (65 mg/kg) and confirmed by biochemical, electrophysiological and histopathological methods. Platelet aggregation was induced with arachidonic acid (AA) and platelet activating factor (PAF), and monitored by using light transmission aggregometery. RESULTS: When platelets were challenged with two different aggregating agents, nimesulide-treated infarcted rabbits showed resistance to platelet aggregation while non-treated infarcted rabbits were found prone to aggregation with both aggregating agents (P < 0.05). CONCLUSION: These results suggest platelet inhibitory effects of nimesulide during experimental ischaemia and infarction in rabbits.
Subject(s)
Isoproterenol/pharmacology , Myocardial Infarction , Platelet Activating Factor/metabolism , Platelet Aggregation/drug effects , Sulfonamides/pharmacology , Animals , Disease Models, Animal , Myocardial Infarction/blood , Myocardial Infarction/drug therapy , Myocardial Infarction/etiology , Myocardial Infarction/pathology , Platelet Aggregation Inhibitors/pharmacology , Platelet Function Tests/methods , Rabbits , Sympathomimetics/pharmacology , Treatment OutcomeABSTRACT
BACKGROUND/AIM: Hypercholesterolemia plays an important role in the development of atherosclerotic disease, which is one of the leading causes of mortality in the world. Previous studies showed that cyclooxygenase (COX) inhibitors could be used in treating hypercholesterolemia. Thepresentstudywas designed to testwhether COX-2 inhibition can improve lipid profiles inhypercholesterolemia. MATERIALS AND METHODS: Rabbits were fed a high-cholesterol diet to produce hypercholesterolemia. The role of COX-2 was evaluated using celecoxib and nimesulide. Rabbits were divided into 4 groups: the first with normal healthy rabbits, second with high-cholesterol diet and pretreatment with saline, third with high-cholesterol diet and pretreatment with celecoxib, and fourth with high-cholesterol diet and pretreatment with nimesulide. Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride levels were measured at 2-week intervals in all the groups. RESULTS: Results show significantly high levels of serum cholesterol, LDL, and triglyceride but low levels of HDL in hypercholesterolemic rabbits pretreated with saline. Rabbits pretreated with nimesulide and celecoxib showed improvement compared to the saline-treated group. CONCLUSION: Improvement of lipid profile by celecoxib in hypercholesterolemic rabbits indicates the detrimental role of COX-2 during atherogenesis. However, the observed effects of nimesulide and celecoxib in hypercholesterolemia may be independent of their ability to inhibit COX-2. Nevertheless, both celecoxib and nimesulide show lipid-lowering potential in experimental hypercholesterolemia.
Subject(s)
Hypercholesterolemia , Pyrazoles/pharmacology , Sulfonamides/pharmacology , Animals , Celecoxib , Cyclooxygenase Inhibitors/pharmacology , Diet, Atherogenic/adverse effects , Diet, High-Fat/adverse effects , Hypercholesterolemia/blood , Hypercholesterolemia/drug therapy , Hypercholesterolemia/etiology , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Male , Rabbits , Treatment Outcome , Triglycerides/bloodABSTRACT
The appearance of pharmaceutical compounds and their bioactive transformation products in aquatic environments is becoming an issue of increasing concern. In this study, the electrochemical oxidation of the widely used antibiotic sulfamethoxazole (SMX) was investigated using a commercial mixed oxide anode (Ti/Ru0.3Ti0.7O2) and a single compartment filter press-type flow reactor. The kinetics of SMX degradation was determined as a function of electrolyte composition, applied current density, and initial pH. Almost complete (98 %) degradation of SMX could be achieved within 30 min of electrolysis in 0.1 mol L(-1) NaCl solution at pH 3 with applied current densities ≥20 mA cm(-2). Nine major intermediates of the reaction were identified by LC-ESI-Q-TOF-MS (e.g., C6H9NO2S (m/z = 179), C6H4NOCl (m/z = 141), and C6H6O2 (m/z = 110)). The degradation followed various routes involving cleavage of the oxazole and benzene rings by hydroxyl and/or chlorine radicals, processes that could occur before or after rupture of the N-S bond, followed by oxidation of the remaining moieties. Analysis of the total organic carbon content revealed that the antibiotic was partially mineralized under the conditions employed and some inorganic ions, including NO3 (-) and SO4 (2-), could be identified. The results presented herein demonstrate the efficacy of the electrochemical process using a Ti/Ru0.3Ti0.7O2 anode for the remediation of wastewater containing the antibiotic SMX.
Subject(s)
Anti-Bacterial Agents/chemistry , Electrolysis/instrumentation , Oxides/chemistry , Sulfamethoxazole/chemistry , Water Pollutants, Chemical/chemistry , Electrodes , Kinetics , Oxidation-Reduction , Titanium/chemistry , Wastewater/chemistryABSTRACT
BACKGROUND: Hordeum vulgare L. (HV or barley) is used by traditional healers to treat various inflammatory and cardiovascular diseases, without the knowledge of pharmacologic rationale behind its actions. This study was designed to explore the potential scientific mechanism(s) that could explain the use of Hordeum vulgare in traditional medicine as a treatment for various inflammatory and cardiovascular diseases. METHODS: A crude extract and its three fractions were prepared from HV and screened for the inhibition of platelet aggregation and various metabolites of cyclooxygenase (COX), lipoxygenase (LOX) pathways of arachidonic acid (AA) metabolism as well as for its effects on certain antioxidant enzymes. Platelet aggregation was monitored using turbidometric principle, AA metabolism through radioimmunoassay and antioxidant enzymes by commercial kits using spectrophotometer. RESULTS: Results show that HV exhibited activities against all human platelet agonists used except adenine diphosphate, and inhibited both COX and LOX pathways of AA metabolism. It also elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). However, these activities were distributed in various fractions of HV. Aqueous fraction was most potent in elevating SOD activity; chloroform fraction had concentrated compounds responsible for COX inhibition while n-hexane seems to possess compounds responsible for LOX inhibition as well as the only fraction enhancing the activity of GPx. CONCLUSIONS: These results suggest the likely mechanisms responsible for observed anti-inflammatory and cardiovascular effects of HV in traditional medicine.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Cardiovascular Agents/pharmacology , Hordeum/chemistry , Plant Extracts/pharmacology , HumansABSTRACT
Human plasma inhibits arachidonic acid metabolism and platelet aggregation. This helps human form a haemostatic control system that prevents the progress of certain aggregatory or inflammatory reactions. Whether this property of plasma is unique to human or extends to other species is not well known. It is speculated that this protective ability of plasma remains evolutionarily conserved in different mammals. In order to confirm this, the effect of plasma from 12 different mammalian species was investigated for its inhibitory potential against arachidonic acid metabolism and platelet aggregation. Metabolism of arachidonic acid by cyclooxygenase and lipoxygenase pathways was studies using radio-immuno assay and thin layer chromatography while platelet aggregation in the plasma of various mammals was monitored following turbedmetric method in a dual channel aggregometer. Results indicate that inhibition of AA metabolism and platelet aggregation is a common feature of plasma obtained from different mammalian species, although there exists large interspecies variation. This shows that besides human, other mammals also possess general protective mechanisms against various aggregatory and inflammatory conditions and this anti-inflammatory property of the plasma is evolutionarily conserved in mammalian species. The most likely candidates responsible for these properties of plasma include haptoglobin, albumin and lipoproteins.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Plasma , Platelet Aggregation Inhibitors/pharmacology , Animals , Arachidonic Acid/metabolism , Biological Evolution , Blood Platelets/drug effects , Blood Platelets/metabolism , Cyclooxygenase Inhibitors/pharmacology , Hemostasis , Humans , Inhibitory Concentration 50 , Lipoxygenase/metabolism , Lipoxygenase Inhibitors/pharmacology , Plasma/metabolism , Platelet Aggregation/drug effects , Prostaglandin-Endoperoxide Synthases/metabolismABSTRACT
Scientific literature shows that inflammation and oxidative stress contribute in the pathogenesis of atherosclerosis. The oxidative stress is the consequence of an imbalance between the free radical generation and elimination. One source of free oxygen radicals is cyclooxygenase (COX)-2 and, therefore, inhibiting the activity of this enzyme is likely to reduce oxidative stress. In the present study an experimental rabbit model of hypercholesterolemia was developed and the effects of COX-2 inhibitors, nimesulide and celecoxib were observed on the activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS). Rabbits were divided into four groups- control, saline, nimesulide and celecoxib, with all groups fed a high cholesterol diet, which only received saline. Low activities of SOD, GPx and TAS were measured in the hypercholesterolemic rabbits pretreated with saline. In the same group, a reciprocal relationship was observed between the LDL-cholesterol concentration and the plasma activities of GPx, SOD and TAS. Rabbits in nimesulide and celecoxib group showed significantly higher activities of SOD, GPx and TAS in hypercholesterolemic rabbits compared to saline group (p<0.05). Our study shows that selective and timely use of COX-2 inhibitors would be useful in preventing the onset and development of atherosclerosis by enhancing antioxidant defence system.
Subject(s)
Cyclooxygenase 2 Inhibitors/therapeutic use , Hypercholesterolemia/metabolism , Oxidative Stress/physiology , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Animals , Antioxidants/metabolism , Celecoxib , Cholesterol, LDL/blood , Disease Models, Animal , Glutathione Peroxidase/metabolism , Hypercholesterolemia/drug therapy , Hypercholesterolemia/etiology , Male , Rabbits , Superoxide Dismutase/metabolismABSTRACT
Acorus calamus L. is used as anti-inflammatory remedy in traditional system of medicine in Pakistan and India. This study was designed to explore the anti-inflammatory mechanism of Acorus calamus L. and its underlying signaling pathways. Aqueous, butanolic and n-hexane fractions of Acorus calamus were tested against cyclooxygenase (COX) and lipoxygenase (LOX) mediated eicosanoids production by arachidonic acid (AA). Butanolic fraction of Acorus calamus, but not the aqueous and n-hexane fractions, inhibited the COX mediated production of thromboxane B2 (TXB2) and liopxygenase product 1 (LP1) -a metabolite of LOX pathway. 12-(hydroxyeicosatetraenoic acid) HETE- another product of the LOX pathway was unaffected by all three fractions. Butanolic fraction of Acorus calamus showed strong inhibition against AA-induced platelet aggregation. Investigation of the underlying signaling pathways revealed that butanolic fraction inhibited phospholipase C (PLC) pathway in platelets, most probably acting on protein kinase C (PKC). Aqueous and n-hexane fractions of Acorus calamus were not effective against any platelet agonist. This study shows that butanolic fraction of Acorus calamus possesses components that inhibit AA metabolism and platelet aggregation through multiple pathways.
Acorus calamus L. se utiliza como remedio anti-inflamatorio en el sistema tradicional de la medicina en Pakistán y la India. Este estudio fue diseñado para explorar el mecanismo anti-inflamatorio de Acorus calamus L. y sus vías de señalización subyacentes. Fracciones acuosa, butanólica y de n-hexano de Acorus calamus se ensayaron frente a la ciclooxigenasa (COX) y de la lipoxigenasa (LOX) mediada por la producción de eicosanoides por el ácido araquidónico (AA). La fracción butanólica de Acorus calamus, pero no las fracciones acuosas y de n-hexano, inhibieron la producción de COX mediada por tromboxano B2 (TXB2) y el producto lipoxigenasa 1 (LP1) - un metabolito de la vía de LOX, 12 - (ácido hidroxieicosatetraenoico) HETE - otro producto de la ruta de LOX no fue afectado por las tres fracciones. La fracción butanólica de Acorus calamus mostró una fuerte inhibición contra la agregación plaquetaria inducida por AA. La investigación de las vías de señalización subyacentes reveló que la fracción butanólica inhibió la fosfolipasa C (PLC) y la vía en las plaquetas, probablemente actuando sobre la proteína quinasa C (PKC). Fracciones acuosas y de n - hexano de Acorus calamus no fueron eficaces contra ningún agonista de plaquetas. Este estudio muestra que la fracción butanólica de Acorus calamus posee componentes que inhiben el metabolismo del AA y la agregación plaquetaria a través de múltiples vías.