Format

Send to

Choose Destination
Toxicol Appl Pharmacol. 1986 Jan;82(1):175-9.

Teratogen metabolism: thalidomide activation is mediated by cytochrome P-450.

Abstract

A metabolite of thalidomide generated by hepatic microsomes inhibited the attachment of tumor cells to concanavalin A-coated polyethylene. Evidence that metabolite formation is mediated by microsomal cytochrome P-450 is presented. Microsomes incubated with thalidomide underwent a type I spectral shift. Metabolite formation was reduced or eliminated by carbon monoxide, SKF-525A, metyrapone, and N-octylamine. Superoxide dismutase treatment had no effect. Metabolite formation required microsomes and NADPH and was dependent on the length of 37 degrees C incubation. The metabolite could be isolated by successive hexane and chloroform extractions. It is likely the inhibitory thalidomide metabolite was generated by a minor cytochrome P-450 species. Whether this thalidomide metabolite is involved in the drug's teratogenic activity remains to be shown.

PMID:
3945939
DOI:
10.1016/0041-008x(86)90449-7
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center