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Doctoral Thesis
DOI
10.11606/T.42.2016.tde-11112016-154538
Document
Author
Full name
Marcelo Luís Monteiro Pereira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Epiphanio, Sabrina (President)
Landgraf, Richardt Gama
Martins, Joilson de Oliveira
Peron, Jean Pierre Schatzmann
Torrecilhas, Ana Cláudia Trócoli
Title in Portuguese
O papel da heme oxigenase 1 na síndrome do desconforto respiratório agudo associada à malária.
Keywords in Portuguese
Heme-oxigenase-1
Malária
Síndrome do desconforto respiratório agudo
Abstract in Portuguese
A malária é uma doença causada pelo parasita do gênero Plasmodium e que foi responsável por cerca de 440.000 mortes em 2015. A síndrome do desconforto respiratório agudo (SDRA) é uma das principais complicações clínicas da malária. O modelo murino DBA/2 reproduz os sinais clínicos da SDRA observados em humanos, quando infectado com o Plasmodium berghei ANKA. Além disso, altos níveis da enzima heme oxigenase 1 (HO-1) foram observados em casos de malária cerebral e em SDRA em humanos. Os nossos dados indicam que os níveis da HO-1 estão aumentados em camundongos que desenvolvem SDRA associada à malária (SDRA-AM). Adicionalmente, a droga indutora de HO-1 (hemina) aumentou a sobrevivência e preveniu a SDRA-AM. Verificou-se também uma redução na permeabilidade pulmonar e nos níveis de VEGF, além de uma melhoria nos parâmetros respiratórios em animais tratados com hemina. Assim sendo, a indução da HO-1 antes do desenvolvimento da SDRA-AM é protetora e assim, a HO-1 pode ser um alvo de novos fármacos, como forma de prevenir o desenvolvimento da SDRA-AM em humanos.
Title in English
The role of heme oxygenase 1 in malaria-associated acute respiratory distress syndrome.
Keywords in English
Acute lung injury / acute respiratory distress syndrome
Heme Oxygenase-1
Malaria
Abstract in English
Malaria is a serious disease, caused by the parasite of the genus Plasmodium, which was responsible to 440,000 deaths in 2015. Acute lung injury/ acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS observed in humans, when infected with Plasmodium berghei ANKA. Additionally, high levels heme oxygenase 1 (HO-1) were reported in cases of cerebral malaria and in ALI/ARDS in humans. Our data have indicated that the HO-1 levels are increased in mice that develop malaria associated ALI/ARDS (MA-ALI/ARDS). Additionally, a HO-1 inducing drug (hemin) increased the survival rate and prevented mice from developing MA-ALI/ARDS in treated mice. Also, there was a decrease in the lung permeability and in lung VEGF levels, and an amelioration of respiratory parameters. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS is protective, making this enzyme a possible target of new drugs to prevent the development of MA-ALI/ARDS in humans.
 
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Release Date
2018-11-16
Publishing Date
2016-11-16
 
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