Walther B, Ghersi-Egea J F, Jayyosi Z, Minn A, Siest G
Neurosci Lett. 1987 Apr 23;76(1):58-62. doi: 10.1016/0304-3940(87)90192-3.
Non-polar, lipid-soluble drugs or xenobiotics are able to cross the blood-brain barrier. The brain cytochrome P-450-dependent monooxygenases may oxidize these molecules to more polar and somewhat hazardous metabolites responsible for neurotoxicity. In order to characterize the cytochrome P-450 dependent aryl hydrocarbon hydroxylase activity in brain subcellular fractions, we used 7-ethoxyresorufin as a substrate, as its O-deethylation reflects specifically the activity of the cytochrome P-450 isoform which metabolizes and is induced by polycyclic aromatic hydrocarbons. The results reported here show that this enzymatic activity occurs in both microsomal and mitochondrial fractions, and that the induction after 3-methylcholanthrene treatment remains limited, thus preventing the formation of high levels of harmful metabolites.
