SULFORAPHANE AND OXOMATE: INHIBITORS OF TPA INDUCED NITRIC OXIDE SYNTHASE (INOS), CYCLOOXYGENASE 2 (COX-2) AND OXIDATIVE STRESS IN MURINE MACROPHAGE AND SKIN MODELS
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Authors
Appledorn, Daniel M.
Issue Date
2000
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Excessive production of nitric oxide and cyclooxygenase 2 (COX-2) are thought
to be causative factors of cellular injury and cancer. Sulforaphane acts as a potent
detoxification enzyme inducer. We tested sulforaphane and oxomate for inhibition of
inducible nitric oxide synthase (iNOS) and COX-2 in cultured mouse macrophage cells.
Western blot analysis of whole cell lysates revealed that sulforaphane mediated a dosedependent
decrease of lipopolysaccharide (LPS)-stimulated iNOS and COX-2
expression. Application of oxomate to LPS-stimulated macrophage cells revealed dosedependent
inhibition of iNOS expression while no inhibition of COX-2 was detected. In
mouse skin models, we found 12-0-Tetradecanoyl-phorbol-13-acetate (TPA) promoted
oxidative stress events~ including altered levels of the reduced glutathione (GSH),
myeloperoxidase and superoxide dismutase, that correlate with cancer. Results show
unaltered levels of GSH in mice pretreated with sulforaphane and oxomate. These
findings suggest that sulforaphane and oxomate have the potential to serve as cancer
chemopreventive agents.
Description
iv, 32 p.
Citation
Publisher
Kalamazoo College
License
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