Anti-pruritic activity of pioglitazone on serotonin-induced scratching in mice: Possible involvement of PPAR-gamma receptor and nitric oxide

Abstract

Pioglitazone is a member of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, particularly used in management of type II diabetes. However it also has effects in some dermatological disorders. The current study was designed to investigate the effects of oral administration of pioglitazone and the association of nitric oxide, in serotonin-induced scratching in mice. In order to produce the scratching activity, serotonin (141nm/site) was administered intradermally in the nape of the neck. Pioglitazone in concentrations of 10, 20, 40 and 80mg/kg, was peroral administered (p.o) as a single dose, 4h before the serotonin injection. PPAR-γ antagonist, GW9662 (2mg/kg, i.p); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester (l-NAME; 1mg/kg, i.p); or a nitric oxide precursor, l-arginine (100mg/kg, i.p.); adminstrated 15min before pioglitazone were analyzed for anti-scratching activity. Results obtained showed that pioglitazone (40 and 80mg/kg, p.o) reduced the scratching in a dose-dependent manner. GW9662 inverted the anti-scratching effect of pioglitazone (80mg/kg). Acute dose of l-NAME (1mg/kg, i.p) also prevented the anti-scratching property of pioglitazone (80mg/kg, p.o); although l-arginine was used in sub-effective dose (100mg/kg, i.p), however it potentiated the anti-scratching behavior when co-injected with pioglitazone (20mg/kg, p.o). The results indicate that acute pioglitazone has an anti-scratching effect on serotonin-induced scratching in mice. It is concluded that anti-scratching outcome of acute pioglitazone is initiated via activation of PPAR-γ receptor and to some extent by the NO pathway.