Effect of phenobarbital treatment on the stereochemistry of the in vitro metabolism of ethylbenzene

Abstract

The metabohsm of ethylbenzene has been studied using isolated subcellular hepatic fractions to ascertain the relationship of enzyme induction to the decreased stereoselectivity of metabolism reported in intact animals. It was observed that both ethylbenzene and 1-phenylethanol were oxidized by microsomal enzymes and that phenobarbital treatment increased the rate of metabolism. Acetophenone, the oxidation product of 1-phenylethanol, was reduced by a soluble reductase which was not altered by phenobarbital treatment. Kinetic studies revealed that phenobarbital treatment produced only quantitative changes in the metabolism of ethylbenzene. No great differences in the metabolism of CRM+)-, (SM-)-, or (RS)-

In vitro metabolism of 2-(5-ethylpyridin-2-yl)benzimidazole

“…Compound No.2 was synthesised and its Rf, Rt, and 1H-NMR spectra (Table I) :i dependent, PB-inducible mixed function oxidase (5.5% with non-induced, 13% with PB-induced rat livers). The conclusion was in agreement with OrmeJohnson (9) and Maylin (10).…”

Flavouring Group Evaluation 16, Revision 2 (FGE.16Rev2): Aromatic ketones from chemical group 21

“…Reduction of acetophenone to 1-phenylethan-1-ol and oxidation of 1phenylethan-1-ol to acetophenone have been reported to occur in rat hepatic subcellular fractions such as cytosol and microsomal preparations in the presence of NAD+ and NADP+ (Hopkins et al, 1972;Maylin et al, 1973). Reduction of acetophenone to 1-phenylethan-1-ol and oxidation of 1phenylethan-1-ol to acetophenone have been reported to occur in rat hepatic subcellular fractions such as cytosol and microsomal preparations in the presence of NAD+ and NADP+ (Hopkins et al, 1972;Maylin et al, 1973).…”

“…Acetophenone [FL-no: 07.004] and 1-phenylethan-1-ol .064] are readily interconvertible and show similar excretion patterns. Reduction of acetophenone to 1-phenylethan-1-ol and oxidation of 1phenylethan-1-ol to acetophenone have been reported to occur in rat hepatic subcellular fractions such as cytosol and microsomal preparations in the presence of NAD+ and NADP+ (Hopkins et al, 1972;Maylin et al, 1973). The oxidation reaction in microsomes is catalysed by two distinct enzymes; the major contribution to the activity is given by the P450 system, as indicated by the inhibition of the oxidase activity by carbon monoxide, its dependence on NADPH and induction by phenobarbital pretreatment (Maylin et al, 1973).…”

Toxicological Profile for Ethylbenzene

“…Numerous studies have demonstrated interactions between ethylbenzene and chemicals that inhibit cytochrome P-450 (e.g., carbon monoxide; Maylin et al 1973), compete with ethylbenzene for metabolism by cytochrome P-450 (e.g., alkylbenzenes, ethanol; Angerer and Lehnert 1979;Elovaara et al 1984;Engstrom et al 1984;Romer et al 1986), or induce cytochrome P-450 (e.g. phenobarbital ;Maylin et al 1973;McMahon and Sullivan 1966).…”

“…phenobarbital ;Maylin et al 1973;McMahon and Sullivan 1966). Competitive inhibition of metabolism by alkylbenzenes, including ethylbenzene, has been introduced into PBPK models of alkylbenzene mixtures and gasoline component mixtures (Dennison et al 2003(Dennison et al , 2004Haddad et al 2001;Tardif et al 1997).…”