The effect of fasudil in an experimental contact hypersensitivity model in mice

In our study, we aimed to investigate the effect of acute and chronic intraperitoneal administration of fasudil at a dose of 40 mg/kg in a contact hypersensitivity mouse model induced by 1-floro-2,4 dinitrobenzene (DNFB) on ear swelling and itching, signs of contact hypersensitivity (CHS), and to determine the role of macrophage polarization in this effect. Ninety female BALB/c mice were divided into two main groups: acute and chronic. Each main group was further subdivided into three subgroups: control, CHS+SF, and CHS-Fasudil. The experimental contact hypersensitivity model was established by sensitizing the mice with a 0.5% DNFB solution (100 µL) applied to the abdominal region on days 0 and 1. Subsequently, a 0.3% DNFB solution (20 µL) was applied to both ears on days 5, 12, and 19 for challenge. Fasudil was administered at 3rd and 24th hour and 24-hour intervals after the DNFB application. Itching behavior and ear thickness were measured in every 24th and 48th hours after challenge. Acute administration of fasudil significantly prevented the increase in ear thickness within 24 hours (p=0.0003). Chronic administration of fasudil also effectively reduced ear thickness at both 24 and 48 hours after the final dose (p<0.0001). Acute fasudil treatment resulted in a significant reduction in the total thickness of the epidermis and dermis (p<0.05), while chronic administration did not affect this parameter. Additionally, acute fasudil treatment increased the number of M2 macrophages (p<0.05), whereas chronic administration showed no significant effect on M2 macrophage numbers. No significant changes were observed in tissue damage scores, itching behavior, or M1 macrophage numbers in either the acute or chronic fasudil groups. In conclusion, our findings suggest that chronic administration of fasudil exerts an anti-inflammatory effect in the experimental contact hypersensitivity model, as evidenced by the reduction in ear thickness.