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

Abstract

ObjectiveThis study investigated the role of L-arginine supplementation to undernourished and Cryptosporidium parvum–infected suckling mice. MethodsThe 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. ResultsL-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. ConclusionThese 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.