Nitric oxide protects against chloroquine resistant Plasmodium yoelii nigeriensis parasites in vitro.
Malaria is a life-threatening disease of global concern. The role of nitric oxide in the clearance of malarial parasites is still under debate. Several reports suggest a possible role for nitric oxide in the protection during initial stages of malarial infection. In the present study, we demonstrate that the nitric oxide in combination with low concentrations of chloroquine controls the parasitaemia in vitro. Activated peritoneal macrophages co-cultured with lipopolysaccharide+interferon-gamma or extracts from Tenospora cordifolia as an immunomodulator promoted nitric oxide production by macrophages. The high concentration of nitric oxide in combination with sub-optimal chloroquine suppressed the parasitaemia in the chloroquine resistant malarial infection. Further, the nitric oxide synthase inhibitor, N(G)-mono-methyl-l-arginine, downregulated nitric oxide production by peritoneal macrophages and the resulting levels of parasitaemia were higher, similar to those of untreated controls. These findings support the proposition that nitric oxide has a crucial role in the control of parasitaemia at the initial periods of blood stage malarial infection.
Immunopharmacology Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India. awasthi@ualberta.ca
Aradhana
A
Awasthi
Ajay
A
Kumar
Shakti N
SN
Upadhyay
Tatsuo
T
Yamada
Yoichi
Y
Matsunaga
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000276:immunology; D004912:Erythrocytes / Q000469:parasitology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D008288:Malaria / Q000276:immunology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D018512:Parasitemia / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology; D010967:Plasmodium yoelii / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000962:Antimalarials; D008070:Lipopolysaccharides; D010936:Plant Extracts; D009569:Nitric Oxide; D007371:Interferon-gamma; D002738:Chloroquine