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1.
PLoS One ; 15(5): e0232987, 2020.
Article in English | MEDLINE | ID: mdl-32407399

ABSTRACT

Escherichia coli and Staphylococcus aureus are important agents of urinary tract infections that can often evolve to severe infections. The rise of antibiotic-resistant strains has driven the search for novel therapies to replace the use or act as adjuvants of antibiotics. In this context, plant-derived compounds have been widely investigated. Cuminaldehyde is suggested as the major antimicrobial compound of the cumin seed essential oil. However, this effect is not fully understood. Herein, we investigated the in silico and in vitro activities of cuminaldehyde, as well as its ability to potentiate ciprofloxacin effects against S. aureus and E. coli. In silico analyses were performed by using different computational tools. The PASS online and SwissADME programmes were used for the prediction of biological activities and oral bioavailability of cuminaldehyde. For analysis of the possible toxic effects and the theoretical pharmacokinetic parameters of the compound, the Osiris, SwissADME and PROTOX programmes were used. Estimations of cuminaldehyde gastrointestinal absorption, blood brain barrier permeability and skin permeation by using SwissADME; and drug likeness and score by using Osiris, were also evaluated The in vitro antimicrobial effects of cuminaldehyde were determined by using microdilution, biofilm formation and time-kill assays. In silico analysis indicated that cuminaldehyde may act as an antimicrobial and as a membrane permeability enhancer. It was suggested to be highly absorbable by the gastrointestinal tract and likely to cross the blood brain barrier. Also, irritative and harmful effects were predicted for cuminaldehyde if swallowed at its LD50. Good oral bioavailability and drug score were also found for this compound. Cuminaldehyde presented antimicrobial and anti-biofilm effects against S. aureus and E. coli.. When co-incubated with ciprofloxacin, it enhanced the antibiotic antimicrobial and anti-biofilm actions. We suggest that cuminaldehyde may be useful as an adjuvant therapy to ciprofloxacin in S. aureus and E. coli-induced infections.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Benzaldehydes/administration & dosage , Ciprofloxacin/administration & dosage , Cymenes/administration & dosage , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Adjuvants, Pharmaceutic/administration & dosage , Adjuvants, Pharmaceutic/pharmacokinetics , Adjuvants, Pharmaceutic/toxicity , Administration, Oral , Benzaldehydes/pharmacokinetics , Benzaldehydes/toxicity , Biofilms/drug effects , Biofilms/growth & development , Biological Availability , Computer Simulation , Cymenes/pharmacokinetics , Cymenes/toxicity , Drug Synergism , Escherichia coli/pathogenicity , Escherichia coli/physiology , Escherichia coli Infections/drug therapy , Humans , In Vitro Techniques , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapy , Staphylococcus aureus/pathogenicity , Staphylococcus aureus/physiology , Urinary Tract Infections/drug therapy
2.
Sci Rep ; 9(1): 3457, 2019 03 05.
Article in English | MEDLINE | ID: mdl-30837573

ABSTRACT

Hydrogen peroxide (H2O2)-based products are effective in tooth whitening; however, their safety is controversial as they may harm patient tissues/cells. These effects are suggested to be concentration-dependent; nonetheless, to date, there are no reports on H2O2-mediated oxidative damage in the gingival tissue, and neither whether this can be detected in gingival crevicular fluid (GCF) samples. We hypothesize that H2O2 whitening products may cause collateral oxidative tissue damage following in office application. Therefore, H2O2 and nitric oxide (NO) levels were investigated in GCF samples obtained from patients undergoing dental bleaching with H2O2 at different concentrations, in a randomized, double-blind, split-mouth clinical trial. A proteomic analysis of these samples was also performed. H2O2-based whitening products promoted inflammation which was detected in GCF samples and lasted for longer following 35% H2O2 bleaching. This included time-dependent changes in NO levels and in the abundance of proteins associated with NO synthesis, oxidative stress, neutrophil regulation, nucleic acid damage, cell survival and/or tissue regeneration. Overall, H2O2-based products used in office promote inflammation irrespective of their concentration. As the inflammation caused by 35% H2O2 is longer, patients may benefit better from using lower concentrations of this bleaching product, as they may result in less tissue damage.


Subject(s)
Gingival Crevicular Fluid/metabolism , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/pharmacology , Tooth Bleaching Agents/metabolism , Tooth Bleaching Agents/pharmacology , Dose-Response Relationship, Drug , Female , Healthy Volunteers , Humans , Hydrogen Peroxide/administration & dosage , Male , Neutrophils/immunology , Neutrophils/metabolism , Oxidative Stress/drug effects , Tooth Bleaching , Tooth Bleaching Agents/administration & dosage
3.
Oxid Med Cell Longev ; 2018: 4904696, 2018.
Article in English | MEDLINE | ID: mdl-29983857

ABSTRACT

Thioredoxin plays an essential role in bacterial antioxidant machinery and virulence; however, its regulatory actions in the host are less well understood. Reduced human Trx activates transient receptor potential canonical 5 (TRPC5) in inflammation, but there is no evidence of whether these receptors mediate bacterial thioredoxin effects in the host. Importantly, TRPC5 can form functional complexes with other subunits such as TRPC4. Herein, E. coli-derived thioredoxin induced mortality in lipopolysaccharide- (LPS-) injected mice, accompanied by reduction of leukocyte accumulation, regulation of cytokine release into the peritoneum, and impairment of peritoneal macrophage-mediated phagocytosis. Dual TRPC4/TRPC5 blockade by ML204 increased mortality and hypothermia in thioredoxin-treated LPS mice but preserved macrophage's ability to phagocytose. TRPC5 deletion did not alter body temperature but promoted additional accumulation of peritoneal leukocytes and inflammatory mediator release in thioredoxin-administered LPS mice. Thioredoxin diminished macrophage-mediated phagocytosis in wild-type but not TRPC5 knockout animals. TRPC5 ablation did not affect LPS-induced responses. However, ML204 caused mortality associated with exacerbated hypothermia and decreased peritoneal leukocyte numbers and cytokines in LPS-injected mice. These results suggest that bacterial thioredoxin effects under LPS stimuli are mediated by TRPC4 and TRPC5, shedding light on the additional mechanisms of bacterial virulence and on the pathophysiological roles of these receptors.


Subject(s)
Escherichia coli/chemistry , Lipopolysaccharides/toxicity , Systemic Inflammatory Response Syndrome/metabolism , TRPC Cation Channels/metabolism , Thioredoxins/therapeutic use , Animals , Hydrogen Peroxide/metabolism , Indoles/toxicity , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Nitric Oxide/metabolism , Phagocytosis/drug effects , Piperidines/toxicity , Systemic Inflammatory Response Syndrome/chemically induced , TRPC Cation Channels/antagonists & inhibitors , Virulence/drug effects
4.
An Acad Bras Cienc ; 90(2 suppl 1): 2161-2166, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29947664

ABSTRACT

Rheumatoid arthritis is a chronic disease of the joints, which causes joint pain and disability. Anaemia is a frequent extra-articular manifestation in rheumatoid arthritis, affecting 30-70% of the patients; presenting a negative impact on patient´s quality of life. Some of the drugs used in rheumatoid arthritis treatment improve anaemia; but little is known on the beneficial effects of the anti-rheumatic leflunomide or the anti-TNFα adalimumab, in this parameter. We investigated the incidence of anaemia in rheumatoid arthritis patients treated or not with leflunomide or adalimumab. We also assessed whether anaemia correlates with disease activity. Anaemia was present in patients who had just been diagnosed with rheumatoid arthritis and had never taken disease modifying agents or biologicals (non-specific therapy group), but not in those taking either leflunomide or adalimumab. The erythrocyte sedimentation rate was increased in patients with non-specific therapy in comparison with those taking either leflunomide or adalimumab. Anaemia correlated with increased erythrocyte sedimentation rate. We suggest that leflunomide and adalimumab may be useful in treating anaemia in patients with rheumatoid arthritis.


Subject(s)
Adalimumab/therapeutic use , Anemia/etiology , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Isoxazoles/therapeutic use , Adult , Female , Humans , Leflunomide , Male , Middle Aged , Treatment Outcome
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