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The role heme oxygenase 1 in malaria-associated acute lung injury

Grant number: 12/10081-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2012
Effective date (End): July 31, 2016
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal researcher:Sabrina Epiphanio
Grantee:Marcelo Luís Monteiro Pereira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:09/53256-7 - Distress syndrome in a murine model associated to the severe malaria: a study of parasite-host interaction, AP.JP


Malaria is a serious disease, caused by the parasite of the genus Plasmodium, which was responsible to 600,000 deaths in 2013. Acute respiratory distress syndrome (ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ARDS in humans, when infected with Plasmodium berghei ANKA. It was demonstrated that the enzyme heme oxygenase 1 (HO-1) prevents mice to develop ARDS. Also, high levels of HO-1 were reported in cases of cerebral malaria and in ARDS in humans. Our data have indicated that the HO-1 mRNA and protein expression is increased in mice that develop malaria associated ARDS (MA-ARDS). Additionally, a HO-1 inducing drug (hemin) prevented mice from developing MA-ARDS, when administered before the beginning of the time window during which MA-ARDS usually develops in this model. Also, there is a decrease in the lung permeability and in lung VEGF levels, which are signs of ARDS, and an amelioration of respiratory parameters in the animals treated with hemin. Therefore, the induction of HO-1 before the development of MA-ARDS seems to be protective and the increased expression of HO-1 on the onset of MA-ARDS development may represent an effort to revert the phenotype of this syndrome by the host. If further data confirm the protective role of HO-1, this enzyme could be a target of new drugs, like the ones based on CORM (CO releasing molecules), to prevent the development of MA-ARDS in humans.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BARATEIRO, ANDRE; PEREIRA, MARCELO L. M.; EPIPHANIO, SABRINA; MARINHO, CLAUDIO R. F. Contribution of Murine Models to the Study of Malaria During Pregnancy. FRONTIERS IN MICROBIOLOGY, v. 10, JUN 19 2019. Web of Science Citations: 1.
PEREIRA, MARCELO L. M.; MARINHO, CLAUDIO R. F.; EPIPHANIO, SABRINA. Could Heme Oxygenase-1 Be a New Target for Therapeutic Intervention in Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome?. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 8, MAY 16 2018. Web of Science Citations: 4.
PEREIRA, MARCELO L. M.; ORTOLAN, LUANA S.; SERCUNDES, MICHELLE K.; DEBONE, DANIELA; MURILLO, OSCAR; LIMA, FLAVIA A.; MARINHO, CLAUDIO R. F.; EPIPHANIO, SABRINA. Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS. Mediators of Inflammation, 2016. Web of Science Citations: 1.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
PEREIRA, Marcelo Luís Monteiro. The role of heme oxygenase 1 in malaria-associated acute respiratory distress syndrome.. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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