Differences in the effects of model inducers of cytochrome P450 on the biotransformation of scoparone in rat and hamster liver

Abstract

The hamster is known to display very high rates of monooxygenase-mediated biotransformation. In comparison with other species little knowledge has been gathered with respect to the nature of its cytochrome P450 enzymes and their respective inducibility. We studied the consequences of induction of P450 enzymes in rats and Syrian golden hamsters using the regioselective oxidative O-demethylation of the coumarin derivative scoparone. This metabolic conversion indicates differential effects of P450 inducers in the rat, in which various types of inducers cause different shifts in the isoscopoletin/scopoletin metabolite ratio (I/S-ratio). Liver microsomes from hamster not treated with P450 inducers oxidized scoparone much more efficiently than liver microsomes of untreated rats. In rat liver microsomes total demethylation rates of scoparone increased upon in vivo treatment with phenobarbital or beta-naphthoflavone. Phenobarbital reduced the I/S-ratio whereas beta-naphthoflavone caused an increase in this ratio. In hamster liver microsomes both phenobarbital and beta-naphthoflavone treatments resulted in a decrease in the I/S ratio. In this species the total scoparone demethylation rate was not much affected by phenobarbital, but beta-naphthoflavone caused a huge increase in over-all scoparone biotransformation. In both species, dexamethasone, isoniazid and clofibrate were much less effective. In contrast to the rat, in the hamster the scoparone biotransformation profile cannot be used to differentiate between phenobarbital- or beta-naphthoflavone-treated animals.

Metabolic Fate of Fraxin Administered Orally to Rats

“…It is well known that phenolic methoxyl groups of aromatic compounds, such as flavonoids and coumarins, are partly demethylated in the liver. [7][8][9][10][11] However, it is interesting to note that both methylated and demethylated metabolites of 4 were produced after hydrolysis of 1 in the rat body.…”

“…In general, orally administered phenolic compounds, particularly those with low polarity, undergo hydroxylation and/or glucuronide and sulfate conjugation primarily by intestinal microflora and secondarily in the liver and other tissues. It is well known that phenolic methoxyl groups of aromatic compounds, such as flavonoids and coumarins, are partly demethylated in the liver. − However, it is interesting to note that both methylated and demethylated metabolites of 4 were produced after hydrolysis of 1 in the rat body.…”

Stimulation of melanogenesis by scoparone in B16 melanoma cells

“…They have recently attracted much attention because of their broad pharmacological activities. Scoparone has been shown to have biological properties that include the inhibition of xanthine oxidase, immunosuppressive effects, vasodilation, lipid lowering activity and antioxidant effects [7][8][9][10][11][12] . However, the direct effect of scoparone alone on the expression of regulatory enzymes involved in melanogenesis has not been reported yet.…”

The Callus of Phaseolus coccineus and Glycine max Biotransform Flavanones into the Corresponding Flavones

“…The efficiency of biotransformation mediated by the cytochrome P450 subunits can be increased by using cytochrome P450 inducers such as beta-naphthoflavone [24,[55][56][57][58].…”