Effects of Hard Metal on the Nitric Oxide Pathway of Rat Lung

Details

• Personal Author:
  Fedan, Jeffery S. ; Rengasamy A
• Description:
  Occupational inhalation of hard metal (HM) induces several disorders including asthma and pulmonary fibrosis. Nitric oxide (NO) is involved in several functions of the lung but the role of NO in HM-induced pulmonary pathophysiology is unknown. We investigated the effect of an industrial HM mixture on the NO pathway in rat lungs. HM was instilled (i.t.) at 2.5 and 5 mg/100 g weight of rat while controls received saline. To compare HM-induced effects with that of lipopolysaccharide (LPS), which induces inducible NOS (iNOS), another group of rats was injected (i.p.) with LPS (0.1 mg/100 g) while others received both LPS and HM. The lungs were removed at 8 and 24 hr and homogenized. NO synthase (NOS) activity in the soluble and particulate fractions was determined by measuring the conversion of L-[14C]argjnine to L-[14C]citrulline. HM or HM plus LPS caused a significant increase of NOS activity in the soluble fraction of rat lungs at 8 and 24 hr, which correlated with the appearance of robust nitrotyrosine immunostaining. However, the particulate NOS activity was decreased in HM-rats and increased in HM plus LPS-treated rats at 8 hr. HM treated rats showed no iNOS protein in Western blots. However, after LPS-treatment alone, iNOS protein appeared and this level was significantly increased by HM at 8 hr which correlated with the iNOS mRNA level as assessed by RT-PCR. These findings suggest that HM-induced alterations in the NO pathway by mechanisms different from that of LPS may be involved in the pathophysiology of hard metal diseases. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Fibrosis Laboratories Lung Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Animal-studies Bronchial-asthma Diseases Hard-metals Laboratory-animals Lung-disorders Oxides Pulmonary-system-disorders Respiratory-system-disorders
• ISSN:
  0892-6638
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  12
• Issue:
  4
• NIOSHTIC Number:
  nn:20056359
• Citation:
  FASEB J 1998 Mar; 12(4)(Pt 1):A490
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  True
• Part Number:
  1
• Source Full Name:
  The FASEB Journal
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8368a0a7e1265b562d3ee60a627a8cfb7ddc3c1431b2e4a4332cb8616d128f8823f5ae6e3c64a4db1885bad6188804bc9543d37bda393bfee59e385f2e9df495
• Download URL:
  https://stacks.cdc.gov/view/cdc/213982/cdc_213982_DS1.pdf
• File Type:
  [PDF - 2.09 MB ]