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1.
Regul Toxicol Pharmacol ; 73(3): 699-705, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26545326

RESUMO

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity.


Assuntos
Anti-Inflamatórios/farmacologia , Edema/prevenção & controle , Óleos Voláteis/farmacologia , Piper , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Pleurisia/prevenção & controle , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Carragenina , Quimiotaxia de Leucócito/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/imunologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Feminino , Dose Letal Mediana , Masculino , Camundongos , Testes para Micronúcleos , Óleos Voláteis/administração & dosagem , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/toxicidade , Fitoterapia , Piper/química , Piper/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta , Óleos de Plantas/administração & dosagem , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/toxicidade , Plantas Medicinais , Pleurisia/induzido quimicamente , Pleurisia/imunologia , Ratos , Ratos Wistar , Medição de Risco , Fatores de Tempo
2.
PLoS One ; 16(2): e0246003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33617571

RESUMO

Dissemination of carbapenem-resistant Klebsiella pneumoniae poses a threat to the successful treatment of bacterial diseases and increases the need for new antibacterial agents development. The objective of this study was to determine the antimicrobial activity of carvacrol against multidrug-resistant K. pneumoniae. Carbapenemase production was detected by MALDI-TOF. The PCR and sequencing showed that the blaKPC-2, blaOXA-48, blaNDM-1, blaCTX-M-8 genes were present in carbapenem-resistant K. pneumoniae strains. The polymyxin-resistant K. pneumoniae strain exhibited alterations in mgrB gene. The antimicrobial activity of carvacrol was evaluated in vitro using broth microdilution and time-kill methods. For this, carbapenem-resistant K. pneumoniae and polymyxin-resistant strains, were evaluated. The in vitro results showed that carvacrol had antimicrobial activity against all isolates evaluated. The survival curves showed that carvacrol eradicated all of the bacterial cells within 4 h. The antimicrobial effect of carvacrol in vivo was determined using a mouse model of infection with Klebsiella pneumoniae carbapenemase (KPC). The treatment with carvacrol was associated with increased survival, and significantly reduced bacterial load in peritoneal lavage. In addition, groups treated with carvacrol, had a significant reduction in the total numbers of white cell and significantly increased of platelets when compared to the untreated group. In vivo and in vitro studies showed that carvacrol regimens exhibited significant antimicrobial activity against KPC-producing K. pneumoniae, making it an interesting candidate for development of alternative treatments.


Assuntos
Antibacterianos/farmacologia , Cimenos/farmacologia , Desenho de Fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Animais , Farmacorresistência Bacteriana/genética , Feminino , Klebsiella pneumoniae/genética , Camundongos
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