title: Arginine decreases Cryptosporidium parvum infection in undernourished suckling mice involving nitric oxide synthase and arginase.
abstract: OBJECTIVE
  This study investigated the role of L-arginine supplementation to undernourished and Cryptosporidium parvum-infected suckling mice.
  
  
  METHODS
  The following regimens were initiated on the fourth day of life and injected subcutaneously daily. The C. parvum-infected controls received L-arginine (200 mmol/L) or phosphate buffered saline. The L-arginine-treated mice were grouped to receive NG-nitro-arginine methyl ester (L-NAME) (20 mmol/L) or phosphate buffered saline. The infected mice received orally 10(6) excysted C. parvum oocysts on day 6 and were euthanized on day 14 at the infection peak.
  
  
  RESULTS
  L-arginine improved weight gain compared with the untreated infected controls. L-NAME profoundly impaired body weight gain compared with all other groups. Cryptosporidiosis was associated with ileal crypt hyperplasia, villus blunting, and inflammation. L-arginine improved mucosal histology after the infection. L-NAME abrogated these arginine-induced improvements. The infected control mice showed an intense arginase expression, which was even greater with L-NAME. L-arginine decreased the parasite burden, an effect that was reversed by L-NAME. Cryptosporidium parvum infection increased urine NO(3)(-)/NO(2)(-) concentrations compared with the uninfected controls, which was increased by L-arginine supplementation, an effect that was also reversed by L-NAME.
  
  
  CONCLUSIONS
  These findings show a protective role of L-arginine during C. parvum infection in undernourished mice, with involvement of arginase I and nitric oxide synthase enzymatic actions.
authors.affiliation: Center for Global Health, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Ibraim C
authors.initials: IC
authors.lastname: Castro
authors.forename: Bruna B
authors.initials: BB
authors.lastname: Oliveira
authors.forename: Jacek J
authors.initials: JJ
authors.lastname: Slowikowski
authors.forename: Bruna P
authors.initials: BP
authors.lastname: Coutinho
authors.forename: Francisco Júlio W S
authors.initials: FJ
authors.lastname: Siqueira
authors.forename: Lourrany B
authors.initials: LB
authors.lastname: Costa
authors.forename: Jesus Emmanuel
authors.initials: JE
authors.lastname: Sevilleja
authors.forename: Camila A
authors.initials: CA
authors.lastname: Almeida
authors.forename: Aldo A M
authors.initials: AA
authors.lastname: Lima
authors.forename: Cirle A
authors.initials: CA
authors.lastname: Warren
authors.forename: Reinaldo B
authors.initials: RB
authors.lastname: Oriá
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D003457:Cryptosporidiosis / Q000150:complications / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D016785:Cryptosporidium parvum; D019587:Dietary Supplements; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000469:parasitology; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000469:parasitology / Q000473:pathology; D008297:Male; D044342:Malnutrition / Q000150:complications / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D018101:Mice, Inbred mdx; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000652:urine; D033661:Oocysts; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D009589:Nitrogen Oxides; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase; D019331:NG-Nitroarginine Methyl Ester