• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
10.11606/D.42.2016.tde-22022016-162207
Document
Author
Full name
Adriana Alejandra Marin Rodriguez
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Katzin, Alejandro Miguel (President)
Krettli, Antoniana Ursine
Santos, Thereza Fonseca Quirico dos
Title in Portuguese
Avaliação do álcool perílico como potencial antimalárico em Plasmodium falciparum e Plasmodium berghei.
Keywords in Portuguese
Plasmodium berghei
Plasmodium falciparum
Álcool perílico
Isoprenilação de proteínas
Isoprenoides
Malaria cerebral experimental
Via intranasal
Via MEP
Abstract in Portuguese
A malária mata mais de um milhão de pessoas por ano, sendo uma das doenças infecciosas mais relevantes e um grande problema de saúde pública. Além disso, o surgimento de cepas resistentes aos quimioterápicos utilizados faz necessário o estudo de novos alvos para tratamentos contra esta doença. No nosso laboratório foi demonstrada a biossíntese de isoprenóides, em P. falciparum pela via MEP. Sabe-se que substâncias inibidoras da biossíntese de isoprenóides, dentre essas os terpenos, apresentam atividade antimalárica. Levando em consideração o anterior, nós avaliamos o potencial antimalárico do álcool perilico (POH) em P. falciparum e P. berghei. Nossos resultados demonstraram que o POH teve efeito inibitório contra o crescimento do P. falciparum in vitro, nas cepas 3D7 e K1 com uma IC50 de 4,8 ± 0,5 μM, e 10,41±2,33 μM, respectivamente. Além disso, o POH não teve efeito tóxico na linhagem celular Vero. Ainda, Comprovamos que o POH inibiu a farnesilação de proteinas entre 20 e 37 KDa de P. falciparum. Por outro lado, os experimentos in vivo não mostraram eficácia do tratamento do POH contra PbGFP em camundongos Balb/c. Em contraste, foi demostrada a eficácia do POH na de malária cerebral experimental (MCE), , indicando uma redução na taxa de incidência da MCE no grupo tratado com POH, comparado o não tratado ( P<0,05). Além disso, o POH reduziu a inflamação no cérebro dos animais tratados, uma vez que teve uma redução significativa na adesão de leucócitos aos vasos cerebrais (P<0.001), como também, o numero de hemorragias foi menor comparados com os animais não tratados. (P<0.0001). Portanto, os resultados obtidos nesta pesquisa abrem novas alternativas no estudo do mecanismo de ação do POH como um terpeno com grande potencial para tratar MC.
Title in English
Evaluation of perillyl alcohol as potential antimalarial in Plasmodium falciparum and Plasmodium berghei.
Keywords in English
Plasmodium berghei
Plasmodium falciparum
Experimental cerebral malária
Intranasally
Isoprenoids
MEP pathway
Perillyl alcohol
Proteins isoprenylation
Abstract in English
Malaria kills over one million people a year worldwide, and is one of the most important infectious diseases and a major public health problem. Furthermore, the emergence of resistant strains to chemotherapeutic agents used, make it necessary to study new targets for treatments against this disease. In our laboratory we have demonstrated the isoprenoids biosynthesis in P. falciparum, by the MEP pathway. It is known that the substances that inhibit isoprenoid biosynthesis, among these terpenes, have antimalarial activity in vitro and in vivo. Considering this, we evaluate the antimalarial potential of PA (POH) in P. falciparum and P. berghei. Our results showed that the POH had inhibitory effect against the growth of strains 3D7 and K1 of P. falciparum in vitro, with an IC50 of 4.8 μM ± 0.5, and 10.41 ± 2.33 μM, respectively. Furthermore, the POH had no toxic effect on cell line Vero. Moreover, the POH proved that inhibited proteins farnesylation from 20 to 37 kDa of P.falciparum. On the other hand, in vivo experiments did not show efficacy on treatment against POH PbGFP in BALB/c mice. In contrast, the effectiveness of POH in the experimental cerebral malaria (MCE) was demonstrated, indicating a reduction in the incidence rate of MCE in the group treated with POH, compared with of untreated animals (P <0.05). In addition, the POH reduced inflammation in the brain of treated animals, since it had a significant reduction in leukocyte adhesion to cerebral vessels (P <0.001), as also the number of bleeding was lower compared to untreated animals (P<0.0001). Therefore, the results obtained in this work provide new alternatives to study the POH's mechanism of action as a terpene with great potential to treat MC.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Release Date
2018-02-21
Publishing Date
2016-02-24
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
Centro de Informática de São Carlos
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2021. All rights reserved.