Effects of NZ-107 on airway inflammation and cell activation in guinea-pigs.

Abstract

The effects of NZ-107 on some airway inflammation models and the generation of superoxide anion (O2-) were studied in guinea-pigs. Airway inflammation was caused by intra-tracheal injection of murine recombinant interleukin-5 (mrIL-5, 15 micrograms/animal), inhalation of platelet-activating factor (PAF, 0.003%) and intra-tracheal injection of leukotriene B4 (LTB4, 10 micrograms/animal). NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) at a dose of 50 mg kg-1, intraperitoneally reduced mrIL-5- and PAF-induced eosinophilia. This compound at a dose of 25 and 50 mg kg-1 also suppressed LTB4-induced eosinophilia and neutrophilia in bronchoalveolar lavage fluid (BALF). On the other hand, prednisolone at a dose of 20 mg kg-1, i.p., prevented the increased number of macrophages, eosinophils and neutrophils induced by mrIL-5, the increased number of eosinophils induced by PAF and the increased number of eosinophils and neutrophils induced by LTB4 in BALF. Furthermore, both drugs reduced mrIL-5- or PAF-induced increase in the number of airway epithelial cells in BALF. The generation of O2- was measured by the method of cytochrome C reduction. NZ-107 (10-100 micrograms mL-1) attenuated PAF- and FMLP-induced O2- production from macrophages and reduced PAF-induced O2- generation by eosinophils but had no effect on that from neutrophils. These results indicate that NZ-107 prevents the increased number of pulmonary eosinophils and airway epithelial cells and the activation of macrophages and eosinophils, suggesting that NZ-107 may be useful as a remedy for airway inflammatory diseases such as bronchial asthma.

• Authors: T Iwama, H Nagai, A Koda
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 45 Issue 4 Pg. 286-91 (Apr 1993) ISSN: 0022-3573 [Print] England
• PMID: 8098369 (Publication Type: Journal Article)

Chemical References

• Interleukin-5
• Leukotriene Antagonists
• Platelet Activating Factor
• Pyridazines
• NZ 107
• Superoxides
• Leukotriene B4
• Prednisolone

Topics

• Animals
• Bronchoalveolar Lavage Fluid (cytology)
• Cell Count (drug effects)
• Eosinophils (drug effects)
• Guinea Pigs
• Interleukin-5 (toxicity)
• Leukocytes (drug effects)
• Leukotriene Antagonists
• Leukotriene B4 (toxicity)
• Lymphocytes (drug effects)
• Macrophages, Alveolar (drug effects)
• Male
• Neutrophils (drug effects)
• Platelet Activating Factor (toxicity)
• Prednisolone (pharmacology)
• Pyridazines (pharmacology, therapeutic use)
• Superoxides (metabolism)