Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Zinc tetrakis(N-methyl-4'-pyridyl) porphyrinato is an effective inhibitor of stimulant-induced activation of RAW 264.7 cells.

Authors
Kang-JL; Pack-IS; Hong-SM; Lee-HS; Hah-JS; Nam-W; Leonard-S; Castranova-V
Source
Toxicol Appl Pharmacol 2001 Apr; 172(2):140-149
NIOSHTIC No.
20021767
Abstract
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.
Keywords
Zinc-compounds; Porphyrins; Stimulants; Fibrosis; Pulmonary-system; Lung-disease; Antioxidants; Silicates; Silica-dusts; Lung-disorders; Pulmonary-system-disorders; Respiratory-system-disorders; In-vivo-studies; Models
Contact
Department of Physiology, College of Medicine, Ewha Womans University, 911-1 Mok-6-dong, Yangcheon-ku, Seoul 158-056, Korea
CODEN
TXAPA9
CAS No.
7440-66-6
Publication Date
20010415
Document Type
Journal Article
Email Address
jihee@mm.ewha.ac.kr.
Fiscal Year
2001
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0041-008X
NIOSH Division
HELD
Source Name
Toxicology and Applied Pharmacology
State
WV
TOP