title: Nitric oxide bioavailability in malaria.
abstract: Rational development of adjunct or anti-disease therapy for severe Plasmodium falciparum malaria requires cellular and molecular definition of malarial pathogenesis. Nitric oxide (NO) is a potential target for such therapy but its role during malaria is controversial. It has been proposed that NO is produced at high levels to kill Plasmodium parasites, although the unfortunate consequence of elevated NO levels might be impaired neuronal signaling, oxidant damage and red blood cell damage that leads to anemia. In this case, inhibitors of NO production or NO scavengers might be an effective adjunct therapy. However, increasing amounts of evidence support the alternate hypothesis that NO production is limited during malaria. Furthermore, the well-documented NO scavenging by cell-free plasma hemoglobin and superoxide, the levels of which are elevated during malaria, has not been considered. Low NO bioavailability in the vasculature during malaria might contribute to pathologic activation of the immune system, the endothelium and the coagulation system: factors required for malarial pathogenesis. Therefore, restoring NO bioavailability might represent an effective anti-disease therapy.
authors.affiliation: La Jolla Bioengineering Institute, 505 Coast Boulevard, Suite 405, La Jolla, CA 92037, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Sobolewski
authors.forename: Irene
authors.initials: I
authors.lastname: Gramaglia
authors.forename: John
authors.initials: J
authors.lastname: Frangos
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
authors.forename: Henri C
authors.initials: HC
authors.lastname: van der Heyde
mesh_terms: D000740:Anemia / Q000097:blood / Q000469:parasitology; D000818:Animals; D001682:Biological Availability; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000378:metabolism / Q000469:parasitology* / Q000517:prevention & control; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010963:Plasmodium falciparum / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D013481:Superoxides; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II