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

Castro, Ibraim C., Oliveira, Bruna B., Slowikowski, Jacek J., Coutinho, Bruna P., Siqueira, Francisco Júlio W.S., Costa, Lourrany B., Sevilleja, Jesus Emmanuel, Almeida, Camila A., Lima, Aldo A.M., Warren, Cirle A., Oriá, Reinaldo B., Guerrant, Richard L.
Nutrition 2012 v.28 no.6 pp. 678-685
Cryptosporidium parvum, arginase, arginine, cryptosporidiosis, esters, histology, hyperplasia, inflammation, malnutrition, mice, nitric oxide synthase, oocysts, parasites, phosphates, suckling, urine, villi, weight gain
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 10⁶ 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 NO₃ ⁻/NO₂ ⁻ 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.