Combination of L-Arginine and L-Norvaline protects against pulmonary fibrosis progression induced by bleomycin in mice

Pulmonary fibrosis (PF) progression may be involved with arginine (Arg) metabolism and immune balance. The present study aimed to explore the effects of L-Arginine (L-Arg) and L-Norvaline (L-Nor) on bleomycin (BLM)-induced PF in mice, meanwhile, and observe dynamic changes of Arg metabolism, immune balance and crosstalk between them in PF progression. Followed intratracheal instillation of BLM or saline, Kunming mice were treated orally with saline, L-Arg, L-Nor and L-Arg + L-Nor three times a day. And the mice were sacrificed on Day 3, 14 and 28 after treatment. Changes of body weight, lung index, lung hydroxyproline and histopathology were analyzed to evaluate the PF degree. Peripheral blood Arg, Citrulline (Cit), Ornithine (Orn) and Proline (Pro), lung NO, NOS and arginase were analyzed to evaluate the Arg metabolism. Peripheral blood Tregs, Th17 and gamma delta T cells were analyzed to evaluate the immune balance. Our data showed that combination of L-Arg and L-Nor dynamically reversed the weight loss, decreased lung index and hydroxyproline, and improved lung histopathological damages induced by BLM. The combination dynamically and significantly rectified Tregs, Th17, gamma delta T and Tregs/Th17 abnormal changes. Meanwhile, these disorders of peripheral blood Arg, Cit, Orn, Pro, Orn/Cit and Pro/Orn, and lung NO, iNOS and TNOS were also improved accordingly. These results demonstrated that combination of L-Arg and L-Nor had inhibitory effects on BLM-induced PF progression, possibly due to their corrective action on immune imbalance, Arg metabolism disorder and crosstalk abnormality in the progression of PF.