Document Detail


Effects of metronidazole analogues on Giardia lamblia: experimental infection and cell organization.
MedLine Citation:
PMID:  23331963     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The chemotherapeutic agents used for the treatment of giardiasis are often associated with adverse side effects and are refractory cases, due to the development of resistant parasites. Therefore the search for new drugs is required. We have previously reported the giardicidal effects of metronidazole (MTZ) and its analogues (MTZ-Ms, MTZ-Br, MTZ-N(3), and MTZ-I) on the trophozoites of Giardia lamblia. Now we evaluated the activity of some giardicidal MTZ analogues in experimental infections in gerbils and its effects on the morphology and ultrastructural organization of Giardia. The giardicidal activity in experimental infections showed ED(50) values significantly lower for MTZ-I and MTZ-Br when compared to MTZ. Transmission electron microscopy was employed to approach the mechanism(s) of action of MTZ analogues upon the protozoan. MTZ analogues were more active than MTZ in changing significantly the morphology and ultrastructure of the parasite. The analogues affected parasite cell vesicle trafficking, autophagy, and triggered differentiation into cysts. These results coupled with the excellent giardicidal activity and lower toxicity demonstrate that these nitroimidazole derivates may be important therapeutic alternatives for combating giardiasis. In addition, our results suggest a therapeutic advantage in obtaining synthetic metronidazole analogues for screening of activities against other infectious agents.
Authors:
Haendel G N O Busatti; Ricardo J Alves; Karla G Santana-Anjos; Frederico F Gil; Marcia C Cury; Marcos A Vannier-Santos; Maria A Gomes
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Diagnostic microbiology and infectious disease     Volume:  75     ISSN:  1879-0070     ISO Abbreviation:  Diagn. Microbiol. Infect. Dis.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8305899     Medline TA:  Diagn Microbiol Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  160-4     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
Affiliation:
Depto. Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CP 31270-901 Belo Horizonte, MG, Brazil; Depto. Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CP 31270-901 Belo Horizonte, MG, Brazil; Depto. Parasitologia, Faculdade de Farmácia, Universidade de Itaúna, Brazil.
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