Arginine decreases Cryptosporidium parvum infection in undernourished suckling mice involving nitric oxide synthase and arginase

Nutrition. 2012 Jun;28(6):678-85. doi: 10.1016/j.nut.2011.09.011. Epub 2012 Jan 20.

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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Arginase / metabolism*
  • Arginine / pharmacology
  • Arginine / therapeutic use*
  • Cryptosporidiosis / complications
  • Cryptosporidiosis / drug therapy*
  • Cryptosporidiosis / parasitology
  • Cryptosporidiosis / pathology
  • Cryptosporidium parvum
  • Dietary Supplements
  • Female
  • Ileum / drug effects
  • Ileum / parasitology
  • Ileum / pathology
  • Inflammation / complications
  • Inflammation / drug therapy
  • Inflammation / parasitology
  • Injections, Subcutaneous
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / parasitology
  • Intestinal Mucosa / pathology
  • Male
  • Malnutrition / complications
  • Malnutrition / drug therapy*
  • Malnutrition / parasitology
  • Malnutrition / pathology
  • Mice
  • Mice, Inbred mdx
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / metabolism*
  • Nitrogen Oxides / urine
  • Oocysts
  • Weight Gain / drug effects*

Substances

  • Nitrogen Oxides
  • Arginine
  • Nitric Oxide Synthase
  • Arginase
  • NG-Nitroarginine Methyl Ester