Metabolism of nonylphenol by rat and human microsomes.
Article Details
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Lee PC, Marquardt M, Lech JJ
Metabolism of nonylphenol by rat and human microsomes.
Toxicol Lett. 1998 Oct 15;99(2):117-26. doi: 10.1016/s0378-4274(98)00153-2.
- PubMed ID
- 9817083 [ View in PubMed]
- Abstract
The in vitro metabolism of [14C]-nonylphenols (NPs) by rat hepatic microsomes in vitro was examined. Product formation was NADPH dependent and inhibited by the cytochrome P450 inhibitors, piperonyl butoxide and SKF525. Hepatic microsomes isolated from various inducer-treated rats (including beta naphthoflavone, phenobarbital, ethanol, dexamethasone, and clofibrate which selectively induce CYP1A, 2B, 2E, 3A and 4A, respectively) all metabolized NPs. Only microsomes from phenobarbital-treated rats exhibited a significantly higher activity towards NPs and showed a different profile of NP metabolites compared to control, untreated rats. Microsomes from human CYP2B6 transfected cells with endogenous NADPH-P450 reductase activity but not microsomes from the non-transfected parent cells metabolized NPs. The metabolism of NPs using microsomes from phenobarbital-treated rats was inhibited by 4-amino-2, 6-dinitro-1-t-butylxylene, a specific CYP2B enzyme inhibitor. Addition of a general anti-CYP2B sera to the reaction mixture attenuated the enzyme activity of microsomes from phenobarbital-treated rats to metabolize NPs. This metabolic reaction was, however, insensitive to a specific anti-CYP2B1 sera that had been shown to inhibit enzyme activities attributed only to CYP2BI suggesting that the CYP2B2 pathway is predominant in NP metabolism. The results indicate that hepatic cytochrome P450 enzyme(s) can metabolize NPs and that CYP2B isozymes are probably involved.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Clofibrate Cytochrome P450 1A1 Protein Humans UnknownInducerDetails Clofibrate Cytochrome P450 2E1 Protein Humans UnknownInducerDetails