Relationship of flavonoid oxidation potential and effect on rat hepatic microsomal metabolism of benzene and phenol.
The effect of several flavonoids on the benzene hydroxylase and phenol hydroxylase activity of rat hepatic microsomes was determined. The electrochemical characteristics of the flavonoids were also determined. The effect of flavonoids on microsomal phenol hydroxylase activity was found to correlate well with the oxidation potential for flavonoid aglycones. Easily oxidized flavonoids inhibited phenol hydroxylase activity with the extent of inhibition correlated to the ease of oxidation. This inhibition exhibited dose-dependent behaviour, with concentrations below 1 microM having no effect. On the other hand, flavonoids with high oxidation potentials increased phenol hydroxylase activity in a dose-independent manner. Hydroxyl substitution at C-7 was required for inhibition of phenol hydroxylase activity independently of the oxidation potential. Glycosylation at either C-7 or C-3 was found to moderate the inhibition of phenol hydroxylase activity. A linear relation was found between the degree of inhibition and the number of sugar residues for glycosylated flavonoids. There was no correlation between electrochemical properties and effect on microsomal benzene hydroxylase activity.
Department of Chemistry, University of Kansas, Lawrence 66045-0049.
H P
HP
Hendrickson
M
M
Sahafayen
M A
MA
Bell
A D
AD
Kaufman
M E
ME
Hadwiger
C E
CE
Lunte
D000818:Animals; D004563:Electrochemistry; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D044948:Flavonols; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats
D005419:Flavonoids; D044948:Flavonols; D006899:Mixed Function Oxygenases; C019765:benzene 1,2-dioxygenase; C022336:phenol 2-monooxygenase