Influence of NO synthase inhibitor L-NAME on parasitemia and survival of Plasmodium berghei infected mice.
Accelerated suicidal death or eryptosis of infected erythrocytes may delay development of parasitemia in malaria. Eryptosis is inhibited by nitric oxide (NO). The present study has been performed to explore, whether inhibition of NO synthase by L-NAME modifies the course of malaria. We show here that L-NAME (>or=10 microM) increased phosphatidylserine exposure of Plasmodium falciparum infected human erythrocytes, an effect significantly more marked than in noninfected human erythrocytes. We further show that parasitemia in Plasmodium berghei infected mice was significantly decreased (from 50% to 18% of circulating erythrocytes 20 days after infection) by addition of 1 mg/ml L-NAME to the drinking water. According to CFSE labelling L-NAME treatment accelerated the clearance of both, noninfected and infected, erythrocytes from circulating blood, but did not significantly extend the life span of infected animals. In conclusion, treatment with L-NAME shortens the life span of circulating erythrocytes and thus delays development of parasitemia during malaria.
Koka
Saisudha
S
Department of Physiology, University of Tübingen, Germany.
Lang
Camelia
C
Niemoeller
Olivier M
OM
Boini
Krishna M
KM
Nicolay
Jan P
JP
Huber
Stephan M
SM
Lang
Florian
F
D000818:Animals; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018512:Parasitemia / Q000188:drug therapy* / Q000201:enzymology; D010962:Plasmodium berghei / Q000187:drug effects*; D015996:Survival Rate
D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester