Effect of Experimental Hepatic Injury on in vitro Drug-Metabolizing Enzyme Activities in the Rat

Willson, Richard A.; Hart, F.E.

doi:10.1016/s0016-5085(19)31767-6

Cited by 11 publications

(1 citation statement)

References 34 publications

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“…The liver is the chief site of biotransformation of variety of xenobiotics where hydrophobic compounds undergo oxygenation or hydroxylation by the cytochrome P450 monooxygenase system (8). Liver damage may, therefore, cause a change in the P450 isozymic population, and alteration in P450 content in drug-induced liver injury has been documented (9). Although each P450 subtype can metabolize a wide variety of compounds, some substrates like aminopyrine, benzo(a)pyrene (BP), and 7-ethoxyresoruhn show specificity for certain P450 isozymes (10).…”

Section: Interaction Of Benzanthrone With Cytochrome P450: Altered Pamentioning

confidence: 99%

Interaction of benzanthrone with cytochrome p450: Altered patterns of hepatic xenobiotic metabolism in rats

Das

Garg

Joshi

et al. 1991

J. Biochem. Toxicol.

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Benzanthrone, an anthraquinone dye intermediate, is commonly used for the synthesis of a number of polycyclic vat and disperse dyes. Our prior studies have shown that benzanthrone can be metabolized by rat hepatic microsomal cytochrome P450 (P450) (Biochem. Int., 18, 1989, 1237). In this study, the interaction of benzanthrone with rat hepatic microsomal P-450 and its effect on xenobiotic metabolism have been investigated. Parenteral administration of benzanthrone (40 mg/kg body weight) for 3, 7, or 21 days caused no change in the relative body weight or organ weight of rats. The levels of P450 were found to be reduced (33%-50%) in all the benzanthrone-exposed animals at all the time periods. In vitro addition of benzanthrone caused a spectral change with oxidized P450 and concentration-dependent reduction in the carbon monoxide spectrum of dithionite-reduced P450. The addition of benzanthrone to hepatic microsomes prepared from phenobarbital-treated rats resulted in spectral changes characterized by an absorbance maximum at 397 nm indicative of type I binding. In vitro addition of benzanthrone showed a concentration-dependent inhibition of hepatic aminopyrine N-demethylase (APD) and ethoxyresorufin-O-deethylase (ERD) activities with respective I50 values of 9.5 x 10(-4) and 8.0 x 10(-5) M. However, the inhibition of aryl hydrocarbon hydroxylase (AHH) even at the highest concentration of benzanthrone (10(-2) M), was of the order of only 29%. In vivo administration of benzanthrone also led to the inhibition of APD, AHH, and ERD activities at all treatment times although the magnitude of inhibition was of a lower order.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Interaction Of Benzanthrone With Cytochrome P450: Altered Pamentioning

confidence: 99%