Abstract
Airway hyperresponsiveness is a key feature of asthma, and attenuating airway hyperresponsiveness is an important part of asthma therapy. In the present study we examined the inhibitory effect of a potent 5-lipoxygenase inhibitor, FR 110302, on airway hyperresponsiveness induced by ozone exposure in guinea pigs and dogs. Respiratory resistance (R rs) was measured by a forced oscillation method. Airway responsiveness was determined from the dose-response curve ofR rs to acetylcholine. Guinea pigs were exposed to 2.5 ppm ozone for 1 h. In a control group of guinea pigs, Δlog PC100 (the index of the ozone-induced airway hyperresponsiveness) was 0.58±0.04 (log mg/ml). Treatment with FR110302 (10 or 100 mg/kg p.o.) significantly diminished Δlog PC100 (10 mg/kg; 0.22±0.10; 100 mg/kg; 0.11±0.06). Dogs were exposed to 3 ppm ozone for 2 h. In a control group of dogs, ΔlogD min (another index of the ozone-induced airway hyperresponsiveness) was 1.24±0.15 (log unit). Treatment with FR110302 (1 or 3.2 mg/kg p.o.) significantly diminished ΔlogD min (1 mg/kg: 0.60±0.18; 3.2 mg/kg: 0.27±0.12). These results suggest that FR110302 may be a useful drug for attenuating airway hyperresponsiveness in asthmatic patients.
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Asano, M., Imai, T., Inoue, H. et al. A 5-lipoxygenase inhibitor, FR110302, inhibits ozone-induced airway hyperresponsiveness in guinea pigs and dogs. Agents and Actions 38, 171–177 (1993). https://doi.org/10.1007/BF01976208
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DOI: https://doi.org/10.1007/BF01976208