Possible Involvement of Nitric Oxide in Antipruritic Effect of Metformin on Chloroquine-Induced Scratching in Mice

Here we investigated the involvement of nitric oxide (NO) pathway in antipruritic effect of metformin in CQ-induced scratching in mice. Metformin (5, 10, 100 and 200 mg/kg, i.p) was injected 4 h prior to CQ injection. A non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 and 10 mg/kg, i.p); or a nitric oxide precursor, L-arginine (10 and 100 mg/kg, i.p.) was administrated 30 min before injection of CQ (400 µg/site, i.d.). A neural NOS inhibitor, 7-nitroinidazole (7NI; 1 and 10 nmol/site, i.d.) concurrently was administrated with 400 µg/site of CQ. The scratching behaviors were recorded following intradermal (i.d.) injection of CQ (200 and 400 µg/site). Our results show that metformin (100 and 200 mg/kg, i.p.) significantly reduces the CQ-induced scratching behavior in a dose-dependent manner. L-arginine inhibits the anti-pruritic effects of metformin. While, injection of L-NAME and 7-NI significantly potentiates the inhibitory effects of sub-effective doses of metformin on the scratching behavior. We conclude that acute injection of metformin significantly inhibits CQ-induced scratching behavior. This effect mediating through inhibition of NO pathway; especially nNOS enzyme.

Keywords:

Scratching , Chloroquine , Nitric Oxide , Metformin , Mice