1. [The mechanism of metabolic denitration of nitroheterocyclic compounds].
- Author
-
Il'iasova VB, Buzukov AA, Tabak M, and Degterev IA
- Subjects
- Animals, Biotransformation drug effects, Cytochrome P-450 Enzyme System metabolism, Electron Spin Resonance Spectroscopy, Hemoglobins metabolism, Heterocyclic Compounds chemistry, Liver enzymology, Liver metabolism, Male, Metyrapone pharmacology, Mice, Nitric Oxide metabolism, Nitro Compounds chemistry, Proadifen pharmacology, Heterocyclic Compounds pharmacokinetics, Nitro Compounds pharmacokinetics
- Abstract
It has been found that denitration of nitroheterocyclic drugs (NHCC) in mouse liver homogenate is one of the pathways of their biotransformation. This process is accompanied by the release of NO and NO-heme iron complex formation. The yield of complex increases linearly with time of NHCC incubation with liver homogenate and depends on NHCC structure. The ESR spectrum of the complex represents a superposition of spectra of NO with hemoglobin and NO with the other heme-containing proteins. NHCC denitration is inhibited by metyrapone, which is an evidence of cytochrome P-450 involvement in their metabolic denitration.
- Published
- 1994