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© Artur Scherf
Scanning Electron Microscopy of Red Blood Cell infected by Plasmodium falciparum.
Publication : Antimicrobial agents and chemotherapy

A novel carbon monoxide-releasing molecule fully protects mice from severe malaria

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Antimicrobial agents and chemotherapy - 12 Dec 2011

Pena AC, Penacho N, Mancio-Silva L, Neres R, Seixas JD, Fernandes AC, Romão CC, Mota MM, Bernardes GJ, Pamplona A

Link to Pubmed [PMID] – 22155828

Antimicrob. Agents Chemother. 2012 Mar;56(3):1281-90

Severe forms of malaria infection, such as cerebral malaria (CM) and acute lung injury (ALI), are mainly caused by the apicomplexan parasite Plasmodium falciparum. Primary therapy with quinine or artemisinin derivatives is generally effective in controlling P. falciparum parasitemia, but mortality from CM and other forms of severe malaria remains unacceptably high. Herein, we report the design and synthesis of a novel carbon monoxide-releasing molecule (CO-RM; ALF492) that fully protects mice against experimental CM (ECM) and ALI. ALF492 enables controlled CO delivery in vivo without affecting oxygen transport by hemoglobin, the major limitation in CO inhalation therapy. The protective effect is CO dependent and induces the expression of heme oxygenase-1, which contributes to the observed protection. Importantly, when used in combination with the antimalarial drug artesunate, ALF492 is an effective adjunctive and adjuvant treatment for ECM, conferring protection after the onset of severe disease. This study paves the way for the potential use of CO-RMs, such as ALF492, as adjunctive/adjuvant treatment in severe forms of malaria infection.

https://www.ncbi.nlm.nih.gov/pubmed/22155828