Zinc Tetrakis(N-Methyl-4′-Pyridyl) Porphyrinato Is an Effective Inhibitor of Stimulant-Induced Activation of RAW 264.7 Cells

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• Personal Author:
  Castranova, Vincent ; Hah JS ; Hong SM ; Kang JL ; Lee HS ; Leonard, Stephanie ; Nam W ; Pack IS
• Description:
  One proposed mechanism for the development of silica-induced fibrosis is prolonged pulmonary inflammation and lung damage resulting from the secretion of reactive mediators from alveolar macrophages. Metalloporphyrins have antioxidative and antiinflammatory activities. However, the molecular basis for the antiinflammatory action of zinc tetrakis(N-methyl-4'-pyridyl) porphyrinato (ZnTMPyP) has not been elucidated. The objective of this study was to determine whether ZnTMPyP exhibited the ability to inhibit the production of reactive oxygen species (ROS), the activation of NF-kappaB, or the secretion of IL-1 in RAW 264.7 cells, and whether such inhibitory activity was related to the ROS-scavenging ability of ZnTMPyP. The results indicate that, although ZnTMPyP is not cytotoxic to RAW 264.7 cells, it is a potent inhibitor in ROS production by RAW 264.7 cells in response to various stimulants, such as silica, zymosan, or phorbol myristate acetate. ZnTMPyP is also effective in reducing stimulant-induced DNA-binding activity of NF-kappaB and silica-induced tyrosine phosphorylation of IkappaB-alpha. ZnTMPyP also inhibits LPS-induced IL-1 production. However, ZnTMPyP exhibits relatively weak ability to directly scavenge hyroxyl or superoxide radicals. On the basis of effective concentrations of ZnTMPyP, these results suggest that ZnTMPyP directly acts as an inhibitor of cellular activation in addition to exhibiting an antioxidant effect. Therefore, it is suggested that further studies concerning the effects of ZnTMPyP using in vivo oxidative stress models or its effects on the cytotoxic process of human diseases associated with lung inflammation and injury are warranted. In addition, ZnTMPyP may be a useful tool to investigate the molecular mechanisms involved in stimulant-induced signal pathways. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Antioxidants Fibrosis Lung Lung Diseases Occupational Health Porphyrins Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Zinc Compounds

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• Keywords:
  Author Keywords: ZnTMPyP IL-1 In-vivo-studies Lung-disease Lung-disorders Models NF-kB Pulmonary-system Pulmonary-system-disorders RAW 264.7 Cells Reactive Oxygen Species Respiratory-system-disorders Silica-dusts Silicates Stimulants Zinc-compounds

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• ISSN:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• 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
• Pages in Document:
  140-149
• Volume:
  172
• Issue:
  2
• NIOSHTIC Number:
  nn:20021767
• Citation:
  Toxicol Appl Pharmacol 2001 Apr; 172(2):140-149
• Contact Point Address:
  Department of Physiology, College of Medicine, Ewha Womans University, 911-1 Mok-6-dong, Yangcheon-ku, Seoul 158-056, Korea
• Email:
  jihee@mm.ewha.ac.kr
• CAS Registry Number:
  Zinc (CAS RN 7440-66-6)
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9ee465c23b774f8462cfd0a3f66705c986e47aecb7ac8106c9c031ac82b3183eefa913a6e5809097466e3b06180449ed0a83a0a6feb07aa360d8a4b4d027abd6
• Download URL:
  https://stacks.cdc.gov/view/cdc/198876/cdc_198876_DS1.pdf
• File Type:
  [PDF - 176.02 KB ]