Nitric Oxide Donor Metallodrug: Single-Inhaler Proposal for Rescue in Acute Allergic Asthma Crises.

Abstract

Allergic asthma is characterized by chronic airway inflammation and recurrent bronchial hyperreactivity, highlighting the need for rapid therapeutic interventions during acute crises. This study aimed to assess the potential of a single-dose administration of the ruthenium nitrosyl complex cis-[Ru(bpy)₂(2-MIM)(NO)](PG₆)₃ (named as FOR811A) as a fast-acting treatment in a murine model of allergic asthma. Female Swiss mice were sensitized with ovalbumin for the induction of asthma and subjected to inhalation challenges. The experimental groups included controls and ovalbumin-sensitized mice receiving FOR811A (0.75 mg/kg) or saline (NaCl 0.9%), both by gavage. Lung tissues were collected for analyses of oxidative damage (nitrite/nitrate and GSH), inflammatory markers (myeloperoxidase, IL-1β, and IL-4), and histological assessment. The results showed that, while FOR811A did not significantly reduce oxidative damage or overall inflammation, it effectively decreased IL-4 levels, indicating a modulation of the Th2 immune response without affecting IL-1β levels (Th1 response). These findings suggest that a single-dose administration of FOR811A may provide a rapid therapeutic effect in allergic asthma crises by promoting smooth muscle relaxation and modulating immune responses. Further research is warranted to explore its clinical utility as a fast-acting rescue medication for acute asthma management.