• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 1
  • Tagged with
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

InvestigaÃÃo dos efeitos centrais e gastroprotetores do isopulegol em camundongos / Evaluation of the central nervous system and gastroprotective effects of isopulegol in mice.

Maria Izabel Gomes Silva 28 August 2009 (has links)
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O isopulegol à um monoterpeno Ãlcool presente no Ãleo essencial de diversas plantas aromÃticas, e tem sido utilizado na manufatura de perfumes com composiÃÃes florais. No presente estudo, inicialmente, foi realizado um screenig farmacolÃgico de aÃÃo central para a investigaÃÃo de possÃveis alteraÃÃes comportamentais induzidas pelo isopulegol. Camundongos Swiss machos foram tratados com isopulegol (25 e 50 mg/kg) ou veÃculo (salina a 0,9% em Tween 0,3%) 30 (i.p.) ou 60 min (v.o.) antes dos experimentos. Flumazenil foi utilizado 15 min antes dos tratamentos com o intuito de investigar a participaÃÃo dos receptores GABAA/BZD nas aÃÃes do isopulegol. A concentraÃÃo de monoaminas e seus metabÃlitos foi tambÃm verificada em corpo estriado apÃs a administraÃÃo aguda de isopulegol. Os resultados dos testes do LCE e hole board sugerem que o isopulegol apresenta provÃvel efeito ansiolÃtico, o qual està relacionado, pelo menos em parte, à modulaÃÃo positiva dos receptores GABAA/BZP. Esse efeito nÃo foi acompanhado de aÃÃo sedativa em baixas doses, o que foi evidenciado pela ausÃncia de diminuiÃÃo de ALE no teste do campo aberto. Os parÃmetros observados no teste do nado forÃado, suspensÃo da cauda e tempo de sono induzido por pentobarbital sugerem que o isopulegol apresenta possÃvel efeito depressor do SNC. Os efeitos centrais observados foram corroborados por uma reduÃÃo na concentraÃÃo de DA e NA, mas nÃo de 5-HT. Com o objetivo de investigar o potencial anticonvulsivante do isopulegol, camundongos foram prÃ-tratados com isopulegol (25, 50, 100 e 200 mg/kg, i.p. ou v.o.) ou veÃculo antes de serem expostos ao modelo de convulsÃo induzida por PTZ (99 mg/kg, s.c.). A participaÃÃo dos receptores GABAA/BZD (utilizando a administraÃÃo prÃvia de flumazenil), bem como se uma possÃvel atividade antioxidante estaria envolvida nas aÃÃes anticonvulsivantes do isopulegol, foram tambÃm investigadas. O isopulegol (100 e 200 mg/kg) apresentou significante atividade anticonvulsivante e bioprotetora contra convulsÃes induzidas pelo PTZ. Nessas doses, a administraÃÃo de isopulegol induziu acentuado efeito sedativo (diminuiÃÃo da ALE em campo aberto). A aÃÃo anticonvulsivante observada foi, possivelmente, relacionada à modulaÃÃo dos receptores GABAA/BZP, uma vez que o prÃtratamento com flumazenil reverteu o prolongamento da latÃncia para as convulsÃes induzidas pelo isopulegol. Propriedades antioxidantes tambÃm foram relacionadas ao efeito anticonvulsivante, desde que o isopulegol preveniu a peroxidaÃÃo lipÃdica, preservou a atividade da catalase e reverteu a reduÃÃo do conteÃdo de GSH induzida pelo PTZ. Com o objetivo de investigar o potencial gastroprotetor do isopulegol em modelo de Ãlcera gÃstrica induzida por etanol e indometacina, os animais receberam isopulegol (25, 50, 100 e 200 mg/kg, v.o.) antes do etanol (0,2 mL, v.o.) ou indometacina (20 mg/kg, v.o.). Uma anÃlise histopatolÃgica de amostras dos estÃmagos foi realizada, bem como possÃveis mecanismos de aÃÃo foram tambÃm investigados. O isopulegol (100 e 200 mg/kg) apresentou significante efeito gastroprotetor em ambos os modelos de Ãlcera induzida por etanol e indometacina, aÃÃo esta corroborada pelo estudo histopatolÃgico. Observou-se que o prÃ-tratamento dos animais com indometacina e glibenclamida reverteu a gastroproteÃÃo induzida pelo isopulegol. O conteÃdo de GSH tambÃm foi preservado pela administraÃÃo prÃvia do isopulegol. Esses resultados sugerem que o efeito gastroprotetor do isopulegol parece ser mediado, pelo menos em parte, pelas prostaglandinas endÃgenas, pela abertura dos canais de KATP e por propriedades antioxidantes referentes ao aumento do conteÃdo de GSH. / Isopulegol is a monoterpene alcohol present in the essential oils of various plants, and has been used in the manufacture of fragrances with blossom compositions. In order to investigate its effects on animal models of CNS actions, isopulegol was administered to male Swiss mice at single doses of 25 and 50 mg/kg 30 (i.p.) or 60 min (p.o.) before the experiments. Control animals received vehicle (saline 0.9% in 0.3% Tween). For investigating the involvement of GABAA/BZP system, flumazenil was utilized 15 min before the treatments. Monoamines and their metabolites concentration were also investigated in striatum of mice after acute administration of isopulegol. The results in EMP and hole board tests suggest possible anxiolytic-like effects from isopulegol, which were reversed by flumazenil pretreatment, indicating probable positive modulation of benzodiazepine-sensitive GABAA receptors. The anxiolytic-like effects were not accompanied by sedation, as reduced locomotion was not observed in open field test. Parameters observed in the forced swimming, tail suspension and pentobarbital sleeping time tests support the idea that isopulegol possibly presents depressant activity on the CNS. The observed central effects were corroborated by DA and NE decreased levels (without changes in 5-HT levels). In order to verify whether isopulegol would be able to exert any protector effect in PTZ-induced convulsions, mice received isopulegol (25, 50, 100 and 200 mg/kg, i.p. or p.o.) or vehicle before PTZ (99 mg/kg, s.c.). The involvement of GABAA/BZP receptors was also investigated by flumazenil pretreatment. Also, it was evaluated whether antioxidant properties from isopulegol would be related to its possible anticonvulsant effect. Results showed that isopulegol (100 and 200 mg/kg) presented anticonvulsant and bioprotective effects against PTZ-induced convulsions. At 100 and 200 mg/kg doses, isopulegol induced marked sedative effect (decreased locomotion in open field test). Flumazenil pretreatment decreased the prolongation of convulsion latency induced by isopulegol, suggesting a possible involvement of direct activation of benzodiazepine site of GABAA. Isopulegol also significantly prevented PTZinduced increase in lipid peroxidation, preserved catalase activity in normal levels, and prevented the PTZ-induced loss of GSH in hippocampus of mice. In order to investigate whether isopulegol would be able to promote gastroprotective effects in ethanol- and indomethacin-induced gastric ulcer models, mice received isopulegol (25, 50, 100 and 200 mg/kg, p.o.) before ethanol (0.2 mL, p.o.) or indomethacin (20 mg/kg, p.o.). A histopathological assessment of stomachs was conducted, as well as possible mechanisms involved in gastroprotective action were also investigated. Isopulegol presented significant gastroprotective effect in both ethanol- and indomethacin-induced ulcer models. This effect was corroborated by the histopathological assay, which showed that pretreatment with isopulegol was able to inhibit the ethanol-induced microscopically alterations. The pretreatment with indomethacin and glibenclamide was able to reverse the gastroprotection induced by isopulegol. The PTZ-induced loss of GSH in stomachs and liver was also preserved by pretreatment with isopulegol. These results suggest that the gastroprotective effects induced by isopulegol appear to be mediated, at least in part, by endogenous prostaglandins, K+ATP channel opening and antioxidant proprieties related to GSH increased.

Page generated in 0.0652 seconds