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1.
PLoS One ; 19(4): e0296607, 2024.
Article in English | MEDLINE | ID: mdl-38626075

ABSTRACT

Tinnitus is a common annoying symptom without effective and accepted treatment. In this controlled experimental study, photobiomodulation therapy (PBMT), which uses light to modulate and repair target tissue, was used to treat sodium salicylate (SS)-induced tinnitus in a rat animal model. Here, PBMT was performed simultaneously on the peripheral and central regions involved in tinnitus. The results were evaluated using objective tests including gap pre-pulse inhibition of acoustic startle (GPIAS), auditory brainstem response (ABR) and immunohistochemistry (IHC). Harmful neural plasticity induced by tinnitus was detected by doublecortin (DCX) protein expression, a known marker of neural plasticity. PBMT parameters were 808 nm wavelength, 165 mW/cm2 power density, and 99 J/cm2 energy density. In the tinnitus group, the mean gap in noise (GIN) value of GPIAS test was significantly decreased indicated the occurrence of an additional perceived sound like tinnitus and also the mean ABR threshold and brainstem transmission time (BTT) were significantly increased. In addition, a significant increase in DCX expression in the dorsal cochlear nucleus (DCN), dentate gyrus (DG) and the parafloccular lobe (PFL) of cerebellum was observed in the tinnitus group. In PBMT group, a significant increase in the GIN value, a significant decrease in the ABR threshold and BTT, and also significant reduction of DCX expression in the DG were observed. Based on our findings, PBMT has the potential to be used in the management of SS-induced tinnitus.


Subject(s)
Cochlear Nucleus , Low-Level Light Therapy , Tinnitus , Rats , Animals , Sodium Salicylate/pharmacology , Tinnitus/chemically induced , Tinnitus/radiotherapy , Neuronal Plasticity/physiology
2.
Sci Rep ; 13(1): 22869, 2023 12 18.
Article in English | MEDLINE | ID: mdl-38129459

ABSTRACT

Soil salinization substantially hampers the growth and development of wheat, potentially leading to plant death in severe cases, thus reducing grain yield and quality. This phenomenon poses a significant threat to food security in China. We investigated the effects of two exogenous plant growth regulators, sodium salicylate and folcisteine, on the wheat physiology and key characteristics under salt stress using hydroponics method. The results indicated that both regulators effectively mitigated the growth inhibition of wheat under salt stress. We assessed morphological and physiological indexes, including antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], peroxidase [POD]) and malondialdehyde (MDA) concentration in wheat after foliar application of sodium salicylate and folcisteine under salt stress. The findings revealed that sodium salicylate was more effective than folcisteine. However, folcisteine showed superior performance in reducing hydrogen peroxide (H2O2) content and superoxide anion (O2-) level compared to sodium salicylate. Simultaneously, Concurrent application of both regulators synergistically enhanced their efficacy, yielding the most favorable outcomes. In addition, this study noted that while the initial effects of these regulators were not pronounced, their sustained application significantly improved wheat growth in stressful condition and alleviated the detrimental impacts of salt stress. This approach could effectively guarantee the food security and production in China.


Subject(s)
Seedlings , Triticum , Sodium Salicylate/pharmacology , Hydrogen Peroxide/pharmacology , Antioxidants/pharmacology , Salt Stress , Superoxide Dismutase/pharmacology , Stress, Physiological
3.
J Orthop Surg Res ; 18(1): 967, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38098039

ABSTRACT

BACKGROUND: Eccentric muscle contraction can cause muscle damage, which reduces the efficiency of exercise. Previous evidence suggested that Sodium salicylate (SS) could improve the repair of aged muscle. This study intends to investigate whether SS can impact skeletal muscle damage caused by eccentric exercise. METHODS: Eccentric treadmill exercise was performed to induce muscle damage in mice. Plasma levels of muscle damage markers were estimated. RT-qPCR was employed for detecting mRNA levels of proinflammatory mediators in murine gastrocnemius muscle. Immunofluorescence staining of laminin/DAPI was utilized for quantifying centrally nucleated myofibers in the gastrocnemius muscle. Western blotting was implemented to examine protein levels of mitsugumin 53 (MG53), matrix metalloproteinase (MMP)-2/9, and NF-κB signaling-related markers. RESULTS: SS administration reduced muscle damage marker production in the plasma and decreased the levels of proinflammatory mediators, MG53 and MMP-2/9 in mice after exercise. SS alleviated the severity of muscle damage in the gastrocnemius of mice after eccentric exercise. SS blocked NF-κB signaling pathway in the gastrocnemius muscle. CONCLUSION: SS administration ameliorates skeletal muscle damage caused by eccentric exercise in the mouse model.


Subject(s)
NF-kappa B , Sodium Salicylate , Mice , Animals , NF-kappa B/metabolism , Sodium Salicylate/pharmacology , Sodium Salicylate/metabolism , Signal Transduction , Muscle, Skeletal/metabolism , Muscle Contraction/physiology , Membrane Proteins/metabolism
4.
Front Cell Infect Microbiol ; 13: 1183959, 2023.
Article in English | MEDLINE | ID: mdl-37614559

ABSTRACT

Introduction: Chronic infections are a major clinical challenge in hard-to-heal wounds and implanted devices. Pseudomonas aeruginosa is a common causative pathogen that produces numerous virulence factors. Due to the increasing problem of antibiotic resistance, new alternative treatment strategies are needed. Quorum sensing (QS) is a bacterial communication system that regulates virulence and dampens inflammation, promoting bacterial survival. QS inhibition is a potent strategy to reduce bacterial virulence and alleviate the negative impact on host immune response. Aim: This study investigates how secreted factors from P. aeruginosa PAO1, cultured in the presence or absence of the QS inhibitor sodium salicylate (NaSa), influence host immune response. Material and methods: In vitro, THP-1 macrophages and neutrophil-like HL-60 cells were used. In vivo, discs of titanium were implanted in a subcutaneous rat model with local administration of P. aeruginosa culture supernatants. The host immune response to virulence factors contained in culture supernatants (+/-NaSa) was characterized through cell viability, migration, phagocytosis, gene expression, cytokine secretion, and histology. Results: In vitro, P. aeruginosa supernatants from NaSa-containing cultures significantly increased THP-1 phagocytosis and HL-60 cell migration compared with untreated supernatants (-NaSa). Stimulation with NaSa-treated supernatants in vivo resulted in: (i) significantly increased immune cell infiltration and cell attachment to titanium discs; (ii) increased gene expression of IL-8, IL-10, ARG1, and iNOS, and (iii) increased GRO-α protein secretion and decreased IL-1ß, IL-6, and IL-1α secretion, as compared with untreated supernatants. Conclusion: In conclusion, treating P. aeruginosa with NaSa reduces the production of virulence factors and modulates major immune events, such as promoting phagocytosis and cell migration, and decreasing the secretion of several pro-inflammatory cytokines.


Subject(s)
Pseudomonas aeruginosa , Quorum Sensing , Animals , Rats , Sodium Salicylate/pharmacology , Titanium , Biological Transport
5.
Sci Rep ; 13(1): 10045, 2023 06 21.
Article in English | MEDLINE | ID: mdl-37344526

ABSTRACT

Unintended side effects linked to the antineoplastic drug cisplatin are a major drawback in its clinical application. The underlying source of these side effects include the generation of reactive oxygen species which are toxic and damaging to tissues and organs. In the present study the anti-inflammatory and antioxidant potential of sodium salicylate was assessed against cisplatin-induced hepatotoxicity in albino rats. Sodium salicylate was used as a model drug and loading into hollow structured porous silica using ultrasound-assisted sol-gel method to produce a nanoemulsion. Transmission Electron Microscopy and Dynamic Light scattering analysis were employed to assess the structural properties and stability of this model. Liver function was assessed by measuring biomarkers including ALT, AST & GGT and oxidant/antioxidant markers including MDA, NO, PON, GSH, MCP1 & AVP in serum or liver tissue. Additionally, blood leukocyte DNA damage was evaluated. Cisplatin significantly altered the normal levels of all biomarkers confirming its hepatotoxic effects. In contrast, treatment with sodium salicylate-loaded silica nanoemulsion significantly restored the levels of these markers. The finding suggests the protective effects of this model drug in preventing cisplatin-induced hepatotoxicity, and therefore may have implications in attenuating cisplatin-induced hepatotoxicity.


Subject(s)
Antineoplastic Agents , Chemical and Drug Induced Liver Injury , Drug-Related Side Effects and Adverse Reactions , Nanoparticles , Rats , Animals , Cisplatin/toxicity , Antioxidants/pharmacology , Antioxidants/metabolism , Sodium Salicylate/metabolism , Sodium Salicylate/pharmacology , Oxidative Stress , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/drug therapy , Antineoplastic Agents/toxicity , Liver/metabolism , Drug-Related Side Effects and Adverse Reactions/metabolism , Biomarkers/metabolism
6.
J Mol Model ; 29(6): 192, 2023 May 31.
Article in English | MEDLINE | ID: mdl-37256432

ABSTRACT

BACKGROUND: Inflammation-provoked disorders including cancer are arbitrated by cyclooxygenase-2 (COX-2). Celecoxib and niflumic acid are among the potent and selective inhibitors of this enzyme while aspirin (acetylsalicylic acid) and sodium salicylate are its non-selective and lesser potent inhibitors. Despite these proven studies, the comparative structural study of these selective and non-selective molecules at atomistic scale in complex state with COX-2 that may answer this differential inhibitory behavior has not been accomplished spotlighting the imperative need of additional research in this area. Thus, this study was framed to provide a strong explanation for the enigma of higher inhibitory activity of celecoxib-niflumic acid duo in comparison to aspirin and sodium salicylate towards COX-2. METHODS: A contemporary approach including advanced molecular docking against COX2, molecular dynamics of receptor-ligand complexes, simulation-trajectory-backed MMGBSA for different time points, radius of gyration (Rg) calculations, and e-pharmacophores approach was employed to attain a rational conclusion. RESULTS: Our findings demonstrated the higher binding affinity of celecoxib and niflumic acid over aspirin and sodium salicylate against COX-2. Although both selective and non-selective COX-2 inhibitors manifested nearly the same stability in the active site of this enzyme but the e-pharmocophoric features found in the case of selective inhibitors scored over non-selective ones. Thus, our findings excluded the differential stability to be the cause of stronger potency of selective inhibitors but attributed their potency to greater number of complementary features present in these inhibitors against the active site of inflammation engendering COX-2.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Sodium Salicylate , Humans , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase 2/chemistry , Celecoxib/pharmacology , Sodium Salicylate/pharmacology , Molecular Dynamics Simulation , Molecular Docking Simulation , Pharmacophore , Niflumic Acid , Aspirin/pharmacology , Inflammation
7.
Int J Mol Sci ; 24(3)2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36768902

ABSTRACT

To meet the current demand of assisted reproduction and animal breeding via superovulation and reduce the impact of hormone drugs, it is necessary to develop new superovulation drugs. This study examined the role of inflammation and steroids in ovulation. Sodium salicylate can regulate inflammation and steroids. However, the effect of sodium salicylate on ovulation has not been studied. In this study, mice were intraperitoneally injected with different concentrations of sodium salicylate for four consecutive days. The effects of sodium salicylate on oocyte quality and on the number of ovulations were examined, and these effects were compared with those of pregnant horse serum gonadotropin (PMSG)/follicle-stimulating hormone (FSH) treatment. We found that low-dose sodium salicylate increased the levels of ovulation hormones and inflammation by promoting the expression of CYP17A1. Sodium salicylate had the same effect as the commonly used superovulation drug PMSG/FSH and reduced the histone methylation level. Sodium salicylate can promote ovulation in mice and Awang sheep. It can greatly decrease the use of hormone drugs, reduce breeding costs and physical impacts, and can thus be used for livestock breeding.


Subject(s)
Gonadotropins, Equine , Sodium Salicylate , Animals , Female , Mice , Pregnancy , Follicle Stimulating Hormone/pharmacology , Gonadotropins, Equine/pharmacology , Horses , Sheep , Sodium Salicylate/pharmacology , Steroids/pharmacology , Superovulation , Cytochrome P450 Family 17/metabolism
8.
Neurosci Lett ; 795: 137041, 2023 01 31.
Article in English | MEDLINE | ID: mdl-36586531

ABSTRACT

Nowadays various analgesic medications are used for the management of acute and chronic pain. Among these opioid and non-steroidal anti-inflammatory drugs stand in the first line of therapy, however, prolonged administration of these substance is generally challenged by development of analgesic tolerance in patients. Therefore, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. In this respect, Taurine, a free amino acid, has been shown to induce significant analgesia at both spinal and peripheral levels through cholinergic mechanisms. In the present study, we used hot-plate analgesic test to investigate how taurine either as a single medication or in combination with sodium salicylate and morphine may affect both acute response to pain and development of analgesic tolerance. The effect of taurine was also tested on morphine withdrawal syndrome. Hyoscine butyl bromide was used to assess the role of muscarinic receptors in taurine-mediated effects. Finally, biochemical assay was done to reveal how the activity of brain acetylcholinesterase may change in relation with muscarinic receptor activity. Results indicated that acute administration of taurine-sodium salicylate combination causes more potent analgesia compared to the use of tau (but not SS alone) and this seems to be mediated via activity of muscarinic receptors in peripheral nervous system. Furthermore, the effect of this combination undergoes less analgesic tolerance during time. Combination of taurine and morphine is an effective strategy to attenuate both morphine analgesic tolerance and dependence and this also seems to depend on activity of muscarinic receptors, however through differential cellular mechanisms.


Subject(s)
Chronic Pain , Morphine , Humans , Acetylcholinesterase , Analgesics/pharmacology , Analgesics, Opioid/pharmacology , Morphine/pharmacology , Sodium Salicylate/pharmacology , Taurine/pharmacology
9.
Eur J Pharmacol ; 928: 175085, 2022 Aug 05.
Article in English | MEDLINE | ID: mdl-35679889

ABSTRACT

Browning, a white to brown-like (beige) adipocyte conversion, offers a promising therapeutic strategy for the treatment of human obesity. In the present study, the effects of sodium salicylate, a nonsteroidal anti-inflammatory drug, on adipocyte browning were investigated. We found sodium salicylate altered the macrophage phenotype to M2 in RAW264.7 cells, mediated by up-regulation of heme oxygenase-1 (HO-1), and sodium salicylate-treated conditioned medium from macrophages (Sal-M2 CM) induced browning of fully differentiated 3T3-L1 adipocytes. Conversely, the conditioned medium obtained from macrophages when treated with sodium salicylate in the presence of either ZnPP (a HO-1 inhibitor) or HO-1 siRNA did not induce browning. In association with macrophage HO-1 induction by sodium salicylate, iron production also increased, and deferoxamine (an iron chelator) blunted the browning effects of Sal-M2 CM, suggesting that iron may play a role in the Sal-M2 CM-induced browning. The in vivo browning effects of sodium salicylate were confirmed in ob/ob mice, whereas in vivo macrophage depletion by clodronate as well as HO-1 blockade by either ZnPP or adeno-associated virus carrying HO-1 shRNA (AAV-HO-1 shRNA) attenuated the browning effects of sodium salicylate. These results reveal sodium salicylate induces browning in vitro and in vivo by up-regulating HO-1 thus promoting M2 polarization.


Subject(s)
Adipocytes, Brown , Adipocytes, White , Heme Oxygenase-1 , Macrophages , Sodium Salicylate , 3T3-L1 Cells , Animals , Culture Media, Conditioned , Heme Oxygenase-1/metabolism , Iron , Membrane Proteins , Mice , RNA, Small Interfering/pharmacology , Sodium Salicylate/pharmacology , Up-Regulation
10.
Neurosci Bull ; 38(1): 69-80, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34235622

ABSTRACT

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.


Subject(s)
Hair Cells, Auditory, Inner , Tinnitus , Animals , Calcium , Exocytosis , Mice , Sodium Salicylate/pharmacology , Tinnitus/chemically induced
11.
Mol Metab ; 56: 101425, 2022 02.
Article in English | MEDLINE | ID: mdl-34954383

ABSTRACT

INTRODUCTION: High-fat diet (HFD)-induced obesity impairs clearance of cholesterol through the Reverse Cholesterol Transport (RCT) pathway, with downregulation in hepatic expression of cholesterol and bile acid transporters, namely ABCG5/8 and ABCB11, and reduced high-density lipoprotein (HDL) cholesterol efflux capacity (CEC). In the current study, we hypothesized that the development of hepatosteatosis, secondary to adipose-tissue dysfunction, contributes to obesity-impaired RCT and that such effects could be mitigated using the anti-inflammatory drug sodium salicylate (NaS). MATERIALS AND METHODS: C57BL/6J mice, fed HFD ± NaS or low-fat diet (LFD) for 24 weeks, underwent glucose and insulin tolerance testing. The 3H-cholesterol movement from macrophage-to-feces was assessed in vivo. HDL-CEC was determined ex vivo. Cytokine secretion from adipose-derived stromal vascular fraction (SVF) cells was measured ex vivo. Liver and HDL proteins were determined by mass spectrometry and analyzed using Ingenuity Pathway Analysis. RESULTS: NaS delayed HFD-induced weight gain, abrogated priming of pro-IL-1ß in SVFs, attenuated insulin resistance, and prevented steatohepatitis (ectopic fat accumulation in the liver). Prevention of hepatosteatosis coincided with increased expression of PPAR-alpha/beta-oxidation proteins with NaS and reduced expression of LXR/RXR-induced proteins including apolipoproteins. The latter effects were mirrored within the HDL proteome in circulation. Despite remarkable protection shown against steatosis, HFD-induced hypercholesterolemia and repression of the liver-to-bile cholesterol transporter, ABCG5/8, could not be rescued with NaS. DISCUSSIONS AND CONCLUSIONS: The cardiometabolic health benefits of NaS may be attributed to the reprogramming of hepatic metabolic pathways to increase fatty acid utilization in the settings of nutritional overabundance. Reduced hepatic cholesterol levels, coupled with reduced LXR/RXR-induced proteins, may underlie the lack of rescue of ABCG5/8 expression with NaS. This remarkable protection against HFD-induced hepatosteatosis did not translate to improvements in cholesterol homeostasis.


Subject(s)
Obesity , Sodium Salicylate , Animals , Cholesterol/metabolism , Liver/metabolism , Metabolic Networks and Pathways , Mice , Mice, Inbred C57BL , Obesity/metabolism , Sodium Salicylate/metabolism , Sodium Salicylate/pharmacology
12.
Neuroscience Bulletin ; (6): 69-80, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-929078

ABSTRACT

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.


Subject(s)
Animals , Mice , Calcium , Exocytosis , Hair Cells, Auditory, Inner , Sodium Salicylate/pharmacology , Tinnitus/chemically induced
13.
Hippocampus ; 31(5): 512-521, 2021 05.
Article in English | MEDLINE | ID: mdl-33580728

ABSTRACT

Sodium salicylate, one of the non-steroidal anti-inflammatory drugs, is widely prescribed in the clinic, but a high dose of usage can cause hyperactivity in the central nervous system, including the hippocampus. At present, the neural mechanism underlying the induced hyperactivity is not fully understood, in particular, in the hippocampus under an in vivo condition. In this study, we found that systemic administration of sodium salicylate increased the field excitatory postsynaptic potential slope and the population spike amplitude in a dose-dependent manner in the hippocampal dentate gyrus area of rats with in vivo field potential extracellular recordings, which indicates that sodium salicylate enhances basal synaptic transmission and neural excitation. In the presence of picrotoxin, a GABA-A receptor antagonist, sodium salicylate failed to increase the initial slope of the field excitatory postsynaptic potential and the amplitude of the population spike in vivo. To further explore how sodium salicylate enhances the neural excitation, we made whole-cell patch-clamp recordings from hippocampal slices. We found that perfusion of the slice with sodium salicylate decreased electrically evoked GABA receptor-mediated currents, increased paired-pulse ratio, and lowered frequency and amplitude of miniature inhibitory postsynaptic currents. Together, these results demonstrate that sodium salicylate enhances the neural excitation through suppressing GABAergic synaptic transmission in presynaptic and postsynaptic mechanisms in the hippocampal dentate gyrus area. Our findings may help understand the side effects caused by sodium salicylate in the central nervous system.


Subject(s)
Hippocampus , Sodium Salicylate , Animals , Dentate Gyrus/physiology , Excitatory Postsynaptic Potentials/physiology , Hippocampus/physiology , Rats , Sodium Salicylate/pharmacology , Synaptic Transmission/physiology
14.
Int J Mol Sci ; 22(3)2021 Jan 21.
Article in English | MEDLINE | ID: mdl-33494399

ABSTRACT

Hard-to-heal wounds are typically infected with biofilm-producing microorganisms, such as Pseudomonas aeruginosa, which strongly contribute to delayed healing. Due to the global challenge of antimicrobial resistance, alternative treatment strategies are needed. Here, we investigated whether inhibition of quorum sensing (QS) by sodium salicylate in different P. aeruginosa strains (QS-competent, QS-mutant, and chronic wound strains) influences biofilm formation and tolerance to silver. Biofilm formation was evaluated in simulated serum-containing wound fluid in the presence or absence of sodium salicylate (NaSa). Biofilms were established using a 3D collagen-based biofilm model, collagen coated glass, and the Calgary biofilm device. Furthermore, the susceptibility of 48-h-old biofilms formed by laboratory and clinical strains in the presence or absence of NaSa towards silver was evaluated by assessing cell viability. Biofilms formed in the presence of NaSa were more susceptible to silver and contained reduced levels of virulence factors associated with biofilm development than those formed in the absence of NaSa. Biofilm aggregates formed by the wild-type but not the QS mutant strain, were smaller and less heterogenous in size when grown in cultures with NaSa compared to control. These data suggest that NaSa, via a reduction of cell aggregation in biofilms, allows the antiseptic to become more readily available to cells.


Subject(s)
Biofilms/drug effects , Biofilms/growth & development , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Silver/pharmacology , Sodium Salicylate/pharmacology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Microbial Viability/drug effects , Pseudomonas Infections/microbiology , Quorum Sensing/drug effects , Virulence Factors
15.
Molecules ; 26(1)2021 Jan 02.
Article in English | MEDLINE | ID: mdl-33401768

ABSTRACT

Human neutrophil elastase (HNE) is used as diagnostic biomarker for inflammation/infection. In this work, 10 ionic liquids (ILs) and 11 ionic liquids active pharmaceutical ingredients (ILs-APIs) were tested to evaluate the inhibition effect on the activity of porcine pancreatic elastase enzyme, frequently employed as a model for HNE. The insertion of ionic liquids in some drugs is useful, as the insertion of ILs with inhibitory capacity will also slow down all processes in which this enzyme is involved. Therefore, a spectrophotometric method was performed to the determination of EC50 values of the compounds tested. EC50 values of 124 ± 4 mM to 289 ± 11 mM were obtained, with the most toxic IL for elastase being tetrabutylammonium acetate and the least toxic 1-butyl-3-methylimidazolium acetate. Moreover, sodium salicylate (raw material) presented the lower and benzethonium bistriflimide the higher EC50 when compared with all the IL-APIs tested. This work provides significant information about the effect of the studied IL and IL-APIs in elastase enzyme activity.


Subject(s)
Ionic Liquids/chemistry , Ionic Liquids/pharmacology , Pancreatic Elastase/antagonists & inhibitors , Serine Proteinase Inhibitors/chemistry , Serine Proteinase Inhibitors/pharmacology , Aniline Compounds/metabolism , Animals , Imidazoles/chemistry , Imidazoles/pharmacology , Ionic Liquids/toxicity , Pancreatic Elastase/metabolism , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Sodium Salicylate/pharmacology , Structure-Activity Relationship , Swine
16.
Hypertension ; 76(1): 267-276, 2020 07.
Article in English | MEDLINE | ID: mdl-32389075

ABSTRACT

Endothelial inflammation and mitochondrial dysfunction have been implicated in cardiovascular diseases, yet, a unifying mechanism tying them together remains limited. Mitochondrial dysfunction is frequently associated with mitochondrial fission/fragmentation mediated by the GTPase Drp1 (dynamin-related protein 1). Nuclear factor (NF)-κB, a master regulator of inflammation, is implicated in endothelial dysfunction and resultant complications. Here, we explore a causal relationship between mitochondrial fission and NF-κB activation in endothelial inflammatory responses. In cultured endothelial cells, TNF-α (tumor necrosis factor-α) or lipopolysaccharide induces mitochondrial fragmentation. Inhibition of Drp1 activity or expression suppresses mitochondrial fission, NF-κB activation, vascular cell adhesion molecule-1 induction, and leukocyte adhesion induced by these proinflammatory factors. Moreover, attenuations of inflammatory leukocyte adhesion were observed in Drp1 heterodeficient mice as well as endothelial Drp1 silenced mice. Intriguingly, inhibition of the canonical NF-κB signaling suppresses endothelial mitochondrial fission. Mechanistically, NF-κB p65/RelA seems to mediate inflammatory mitochondrial fission in endothelial cells. In addition, the classical anti-inflammatory drug, salicylate, seems to maintain mitochondrial fission/fusion balance against TNF-α via inhibition of NF-κB. In conclusion, our results suggest a previously unknown mechanism whereby the canonical NF-κB cascade and a mitochondrial fission pathway interdependently regulate endothelial inflammation.


Subject(s)
Dynamins/physiology , Endothelial Cells/physiology , Endothelium, Vascular/pathology , Mitochondrial Dynamics/physiology , NF-kappa B/metabolism , Vasculitis/physiopathology , 3T3 Cells , Animals , Aorta/cytology , Cell Adhesion , Cells, Cultured , Dynamins/antagonists & inhibitors , Dynamins/genetics , Endothelial Cells/drug effects , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Membrane Proteins/physiology , Mice , Mitochondrial Proteins/physiology , Mutation, Missense , Phosphorylation , Phosphoserine/metabolism , Protein Processing, Post-Translational , Proteome , RNA Interference , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Rats , Sodium Salicylate/pharmacology , Tumor Necrosis Factor-alpha/pharmacology , Vascular Cell Adhesion Molecule-1/biosynthesis , Vascular Cell Adhesion Molecule-1/genetics
17.
J Med Microbiol ; 69(5): 767-780, 2020 May.
Article in English | MEDLINE | ID: mdl-32320374

ABSTRACT

Introduction. An important factor for delayed healing of chronic wounds is the presence of bacteria. Quorum sensing (QS), a cell density-dependent signalling system, controls the production of many virulence factors and biofilm formation in Pseudomonas aeruginosa.Aim. Inhibition by sodium salicylate (NaSa) of QS-regulated virulence expression was evaluated in QS-characterized clinical wound isolates of P. aeruginosa, cultured in serum-containing medium.Methodology. Fourteen clinical P. aeruginosa strains from chronic wounds were evaluated for the production of QS signals and virulence factors. Inhibition of QS by NaSa in P. aeruginosa clinical strains, wild-type PAO1 and QS reporter strains was evaluated using in vitro assays for the production of biofilm, pyocyanin, siderophores, alkaline protease, elastase and stapholytic protease.Results. Six clinical strains secreted several QS-associated virulence factors and signal molecules and two were negative for all factors. Sub-inhibitory concentrations of NaSa downregulated the expression of the QS-related genes lasB, rhlA and pqsA and reduced the secretion of several virulence factors in PAO1 and clinical strains cultured in serum. Compared to serum-free media, the presence of serum increased the expression of QS genes and production of siderophores and pyocyanin but decreased biofilm formation.Conclusions. Pseudomonas aeruginosa from chronic wound infections showed different virulence properties. While very few strains showed no QS activity, approximately half were highly virulent and produced QS signals, suggesting that the targeting of QS is a viable and relevant strategy for infection control. NaSa showed activity as a QS-inhibitor by lowering the virulence phenotypes and QS signals at both transcriptional and extracellular levels.


Subject(s)
Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/physiology , Quorum Sensing/drug effects , Sodium Salicylate/pharmacology , Chronic Disease , Humans , Pseudomonas aeruginosa/isolation & purification , Virulence/drug effects , Virulence Factors/genetics
18.
PLoS One ; 15(2): e0214267, 2020.
Article in English | MEDLINE | ID: mdl-32106264

ABSTRACT

The development of alternatives to antibiotics is crucial to limiting the incidence of antimicrobial resistance, especially in prophylactic and metaphylactic use to control post-weaning diarrhea (PWD). Feed additives, including bioactive compounds, could be a promising alternative. This study aimed to test two bioactive compounds, sodium salicylate (SA) and a chestnut extract (CE) containing hydrolysable tannins, on the occurrence of PWD. At weaning, 72 piglets were assigned to four treatments that combined two factors: CE supplementation (with 2% of CE (CE+) or without (CE-)) and SA supplementation (with 35 mg/kg BW of SA (SA+) or without (SA-)). Then, 4 days after weaning, all piglets were infected with a suspension at 108 CFU/ml of enterotoxigenic Escherichia coli (ETEC F4ac). Each piglet had free access to an electrolyte solution containing, or not, SA. This SA supplementation was administered for 5 days (i.e., from the day of infection (day 0) to 4 days post-infection (day 4). During the 2 weeks post-infection, supplementation with SA had no effect (P > 0.05) on growth performances nor on fecal scores. A significant SA × time interaction (P < 0.01) for fecal scores and the percentage of diarrhea indicated that piglets with SA did not recover faster and did have a second episode of diarrhea. In contrast to SA treatment, inclusion of CE increased (P < 0.05) growth performances and feed intake. In the first week post-infection, CE decreased (P < 0.001) the overall fecal scores, the percentage of piglets with diarrhea, the days in diarrhea, and ETEC shedding in the feces. There was a SA×CE interaction (P < 0.05) for ETEC shedding, suggesting a negative effect of combining SA with CE. This study highlighted that, in contrast to SA, CE could represent a promising alternative to antibiotics immediately after weaning for improving growth performance and reducing PWD.


Subject(s)
Diarrhea/veterinary , Enteropathogenic Escherichia coli/drug effects , Plant Extracts/therapeutic use , Sodium Salicylate/therapeutic use , Swine Diseases/drug therapy , Animals , Bacterial Shedding , Diarrhea/drug therapy , Diarrhea/microbiology , Fagaceae/chemistry , Plant Extracts/pharmacology , Sodium Salicylate/pharmacology , Swine , Swine Diseases/microbiology
19.
Neuroscience ; 426: 129-140, 2020 02 01.
Article in English | MEDLINE | ID: mdl-31846750

ABSTRACT

Hyperacusis, an exaggerated, sometimes painful perception of loudness even for soft sounds, is a poorly understood distressing condition. While the involvement of modified gain of central auditory neurons and the influence of nonauditory brain regions are well-documented, the issue of where in the auditory system these abnormalities arise remains open, particularly when hyperacusis comes without sensorineural hearing loss. Here we used acute intraperitoneal administration of sodium salicylate (150 mg/kg) in rats, enough to produce > 10-dB decrease in acoustic startle threshold with mild hearing loss at low frequencies (<10 kHz). Anesthesia, necessary for middle-ear-reflex (MEMR) threshold measurements, abolished the olivocochlear efferent reflex but not the MEMR acting on frequencies < 10 kHz, and its mean threshold increased from 55 dB SPL in controls to 80 dB SPL in salicylate-treated animals 60-90 minutes after injection, with an about 3-dB increase in acoustic energy reaching the cochlea. The mean latencies of auditory brainstem-evoked responses (ABR) conspicuously decreased after salicylate, by 0.25 millisecond at 6 kHz at every level, a frequency-dependent effect absent above 12 kHz. A generic model of loudness based upon cross-frequency coincidence detection predicts that with such timing changes, a transient sound may seem as loud at <40 dB SPL as it does in controls at >60 dB SPL. Candidate circuits able to act at the same time on the startle reflex, the MEMR and ABRs may be serotoninergic, as salicylate is known to increase brain serotonin and 5-HT neurons participate in MEMR and ABR circuits.


Subject(s)
Evoked Potentials, Auditory, Brain Stem/drug effects , Hyperacusis/physiopathology , Animals , Auditory Cortex/drug effects , Auditory Threshold/drug effects , Hearing/drug effects , Hyperacusis/chemically induced , Inferior Colliculi/drug effects , Male , Rats, Sprague-Dawley , Reflex, Startle/physiology , Sodium Salicylate/pharmacology
20.
J Dairy Sci ; 102(11): 9767-9780, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31495615

ABSTRACT

Our objective was to determine the effects of uncouplers of oxidative phosphorylation on feeding behavior of lactating dairy cows. We hypothesized that uncouplers of oxidative phosphorylation would increase meal size and meal length and performed 2 experiments to test our hypothesis. In experiment 1, 4 late-lactation cows (345 ± 48.4 d in milk; mean ± SD) were administered a daily intrajugular injection of either 10 mg/kg of BW0.75 of 2,4-dinitrophenol methyl ether (DNPME) and propylene carbonate or propylene carbonate (control; CON) in a crossover design with 2-d periods. In experiment 2, 8 early-lactation cows (11.3 ± 0.89 d in milk) were administered a daily intrajugular injection via jugular catheter of either 50 mg/kg of BW of sodium salicylate (SAL) and saline or saline (control; CON) in a crossover design with 1-d periods. Feeding behavior was recorded by a computerized data acquisition system and analyzed for the first 4 h after access to feed within 15 min of treatment for both experiments. Neither DNPME nor SAL affected meal size over the first 4 h after access to feed. However, DNPME increased meal length by 6.4 min (26.3 vs. 19.9 min) and tended to decrease the number of meals (2.55 vs. 2.78 meals/4 h) over the first 4 h after access to feed compared with CON. Both DNPME and SAL decreased eating rate over the first 4 h after access to feed compared with their respective controls (0.10 vs. 0.12 kg/min for DNPME vs. CON; 0.06 vs. 0.07 kg/min for SAL vs. CON). Lack of treatment effects on meal size may have been caused by increased rate of oxidation of fuels compensating for the disruption of oxidative phosphorylation.


Subject(s)
Cattle/physiology , Feeding Behavior/drug effects , Oxidative Phosphorylation/drug effects , Sodium Salicylate/pharmacology , Uncoupling Agents/pharmacology , Animal Feed/analysis , Animals , Breast Feeding , Cross-Over Studies , Diet/veterinary , Female , Lactation/drug effects , Liver/chemistry , Milk , Sodium Salicylate/administration & dosage , Uncoupling Agents/administration & dosage
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