Silver Nanoparticles Attenuate Histamine-Induced Pruritus via Modulation of the Nitric Oxide/iNOS Signaling Pathway in Mice.

Abstract

Background: Pruritus is an unpleasant cutaneous sensation that provokes scratching behavior and is associated with numerous inflammatory and dermatological disorders. Histamine is a major mediator of pruritus and contributes to the activation of inflammatory and oxidative stress pathways. Silver nanoparticles (Ag-NPs) possess well-documented anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. The present study investigated the antipruritic effects of Ag-NPs and the involvement of the nitric oxide (NO) signaling pathway in histamine-induced pruritus in mice.

Methods: Silver nanoparticles were synthesized using a green synthesis approach and characterized by UV-Vis spectroscopy, FTIR, and SEM analyses. Histamine-induced pruritus was established in male NMRI mice by intradermal injection of histamine (400 µg) into the shaved nape of the neck. Ag-NPs were administered intraperitoneally at doses of 1, 1.5, and 2 mg/kg. To investigate the role of nitric oxide signaling, mice received the nitric oxide synthase inhibitors Nω-Nitro-L-arginine methyl ester (L-NAME, 1 mg/kg) or aminoguanidine (AG, 200 mg/kg) prior to histamine administration. Scratching behavior was recorded, while oxidative stress markers, nitric oxide levels, nerve growth factor (NGF), inducible nitric oxide synthase (iNOS) expression, and histopathological changes were evaluated.

Results: Histamine administration increased scratching behavior, nitric oxide production, nerve growth factor (NGF) levels, oxidative stress, and iNOS gene expression in mouse skin tissue. Treatment with Ag-NPs significantly reduced histamine-induced scratching and attenuated nitric oxide production. Ag-NPs also improved antioxidant status by increasing glutathione, glutathione S-transferase, and catalase levels while reducing lipid peroxidation. Furthermore, Ag-NPs treatment significantly decreased NGF levels and suppressed iNOS mRNA expression. Histopathological examination revealed marked improvement in skin architecture and reduced tissue damage in Ag-NP-treated groups. The antipruritic effects of Ag-NPs were further enhanced in combination with nitric oxide synthase inhibitors, suggesting the involvement of the NO/iNOS signaling pathway.

Conclusion: Silver nanoparticles exhibit antipruritic activity against histamine-induced pruritus in mice. Their protective effects are associated with suppression of the NO/iNOS pathway, reduction of oxidative stress, modulation of NGF expression, and attenuation of inflammatory responses. These findings suggest that Ag-NPs may represent a promising therapeutic strategy for the management of pruritic disorders.