Research

Effects of nitric oxide synthase inhibitor ω-Nitro-L-Arginine Methyl Ester, on silica-induced inflammatory reaction and apoptosis

He Wang¹ and James Leigh²

¹  Discipline of Public Health, University of Adelaide, 10 Pulteney Street, Adelaide, 5005 SA, Australia

²  School of Public Health, University of Sydney, Sydney, 2006 NSW, Australia

author email corresponding author email

Particle and Fibre Toxicology 2006, 3:14doi:10.1186/1743-8977-3-14

Published:	7 November 2006

Abstract

Background

Although nitric oxide is overproduced by macrophages and neutrophils after exposure to silica, its role in silica-induced inflammatory reaction and apoptosis needs further clarification. In this study, rats were intratracheally instilled with either silica suspension or saline to examine inflammatory reactions and intraperitoneally injected with ω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthases, or saline to examine the possible role of nitric oxide production in the reaction.

Results

Results showed that silica instillation induced a strong inflammatory reaction indicated by increased total cell number, number of neutrophils, protein concentration and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF). There were no significant differences in these indices between silica-instilled groups with and without L-NAME injection (p > 0.05) except LDH level. The results also showed that apoptotic leucocytes were identified in BALF cells of silica-instilled groups whereas no significant difference was found between silica-instilled groups with and without L-NAME injection in the apoptotic reaction (p > 0.05). Silica instillation significantly increased the level of BALF nitrite/nitrate and L-NAME injection reduced this increase.

Conclusion

Intratracheal instillation of silica caused an obvious inflammatory reaction and leucocyte apoptosis, but these reactions were not influenced by intraperitoneal injection of L-NAME and reduced production of NO. This supports the possibility that silica-induced lung inflammation and BALF cell apoptosis are via NO-independent mechanisms.