Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak

Irene Gramagliaid, Joyce Velez, Yu Sun Chang, Wilson Caparros-Wanderley, Valery Combes, Georges Grau, Monique Stins, Henri C. Van Der Heyde

Research output: Contribution to journalArticle

Abstract

Clinical and model studies indicate that low nitric oxide (NO) bioavailability due in part to profound hypoargininemia contributes to cerebral malaria (CM) pathogenesis. Protection against CM pathogenesis may be achieved by altering the diet before infection with Plasmodium falcIParum infection (nutraceutical) or by administering adjunctive therapy that decreases CM mortality (adjunctive therapy). This hypothesis was tested by administering citrulline or arginine in experimental CM (eCM). We report that citrulline injected as prophylaxis immediately post infection (PI) protected virtually all mice by ameliorating (i) hypoargininemia, (ii) urea cycle impairment, and (iii) disruption of blood brain barrier. Citrulline prophylaxis inhibited plasma arginase activity. Parasitemia was similar in citrulline- And vehicle control-groups, indicating that protection from pathogenesis was not due to decreased parasitemia. Both citrulline and arginine administered from day 1 PI in the drinking water significantly protected mice from eCM. These observations collectively indicate that increasing dietary citrulline or arginine decreases eCM mortality. Citrulline injected IP on day 4 PI with quinine-injected IP on day 6 PI partially protected mice from eCM; citrulline plus scavenging of superoxide with pegylated superoxide dismutase and pegylated catalase protected all recIPients from eCM. These findings indicate that ameliorating hypoargininemia with citrulline plus superoxide scavenging decreases eCM mortality.

Original languageEnglish (US)
Article numbere0213428
JournalPloS one
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2019

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Cerebral Malaria
citrulline
Citrulline
blood vessels
Blood Vessels
Urea
urea
mice
infection
arginine
Arginine
Infection
pathogenesis
Parasitemia
parasitemia
Scavenging
Superoxides
superoxide anion
Mortality
disease control

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Gramagliaid, I., Velez, J., Chang, Y. S., Caparros-Wanderley, W., Combes, V., Grau, G., ... Van Der Heyde, H. C. (2019). Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak. PloS one, 14(3), [e0213428]. https://doi.org/10.1371/journal.pone.0213428

Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak. / Gramagliaid, Irene; Velez, Joyce; Chang, Yu Sun; Caparros-Wanderley, Wilson; Combes, Valery; Grau, Georges; Stins, Monique; Van Der Heyde, Henri C.

In: PloS one, Vol. 14, No. 3, e0213428, 01.03.2019.

Research output: Contribution to journalArticle

Gramagliaid, I, Velez, J, Chang, YS, Caparros-Wanderley, W, Combes, V, Grau, G, Stins, M & Van Der Heyde, HC 2019, 'Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak', PloS one, vol. 14, no. 3, e0213428. https://doi.org/10.1371/journal.pone.0213428
Gramagliaid, Irene ; Velez, Joyce ; Chang, Yu Sun ; Caparros-Wanderley, Wilson ; Combes, Valery ; Grau, Georges ; Stins, Monique ; Van Der Heyde, Henri C. / Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak. In: PloS one. 2019 ; Vol. 14, No. 3.
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