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1.
Cell Mol Biol (Noisy-le-grand) ; 69(3): 198-206, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37300667

RESUMO

Klebsiella pneumoniae producing extended-spectrum ß-lactamases (ESBL) continues to pose huge therapeutic challenges in the treatment of infections, primarily urinary infections, due to its multidrug resistance to antibiotics. Therefore, there is a need for research on this topic to investigate ways to reduce the spread of antibiotic resistance, identify novel therapeutic approaches to treat these infections and gain a better understanding of the mechanisms of resistance. In this context, this study aimed to analyze the chemical composition of essential oils (EOs) of Thymus algeriensis, Syzygium aromaticum, and Eucalyptus globulus and assess their activity against K. pneumoniae ESBL strains, as well as the interaction type between these EOs and antibiotics used for the treatment of K. pneumoniae ESBL infections. The composition of the EOs was determined by gas chromatography-mass spectrometry (GC-MS). The activity of EOs was tested using the disc diffusion and liquid microdilution methods. The type of interaction between EOs and antibiotics was studied using the agar disk diffusion and chessboard methods. The analysis of the EO of T. algeriensis showed that the main compounds were thymol (23.14%), linalool (18.44%), and p-cymene (16.17%). The main constituents of EO of E. globulus were eucalyptol (54.29%), α-pinene (17.32%), aromadendrene (7.02%), and pinocarveol (6.32%). As for the EO of S. aromaticum, the major constituents were eugenol (80.46%) and eugenol acetate (16.23%). Results of the activity tests showed that all three EOs were active against the tested strains, with inhibition diameters ranging from 7.39±0.44mm to 32.4±1.05mm and minimum inhibitory concentrations (MICs) varying from 2 to 441.5±5.66 mg/ml. A synergistic interaction was obtained between amoxicillin-clavulanic acid and T. algeriensis EO against two strains of K. pneumoniae ESBL. These results demonstrate the potential of our EOs to inhibit multi-resistant pathogenic ESBL strains, as well as their synergistic interaction with antibiotics used in therapy, which could be an alternative to the use of antibiotics alone in treatment to fight against these multi-resistant pathogenic bacteria.


Assuntos
Antibacterianos , Óleos Voláteis , Antibacterianos/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Klebsiella pneumoniae , Eugenol , Timol , Bactérias , Testes de Sensibilidade Microbiana
2.
Neurotox Res ; 40(2): 564-572, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35366203

RESUMO

Janus-activated kinases (JAKs) are well known to play a physiological as well as pathological role in several disease conditions such as autoimmune disorders. The present study evaluated the therapeutic potential of CP690550 (pan-JAK inhibitor) in 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP) model of Parkinson's disease. Intrastriatal administration of MPTP (30 micromol in 2 microl) produced a significant alteration in behavioural (bar test and block test). Biochemical investigations in serum and brain homogenate revealed a significant alteration in the JAK-mediated cytokine levels. MPTP administration also showed significant imbalance of inflammatory (increased TNF-α, IL-6 and NF-κb) versus anti-inflammatory cytokines (decreased IL-10 levels). MPTP-treated brain sections revealed alteration in the tissue architecture as well as undifferentiated bodies of varying contour and lesions. Chronic administration of CP690550 (3 and 10 mg/kg, po) for 7 days significantly reversed the behavioural, biochemical and histological alterations induced by MPTP. In conclusion, the findings of the present study govern the possible therapeutic potential of CP690550 in MPTP-treated mice and thus highlight the therapeutic potential of JAK inhibitors in treatment of Parkinson's disease.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Piperidinas , Pirimidinas , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Citocinas , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Doença de Parkinson Secundária , Piperidinas/farmacologia , Pirimidinas/farmacologia
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