Metabolism in vivo of dioxane: Effect of inducers and inhibitors of hepatic mixed-function oxidases
Woo, YT; Argus, MF; Arcos, JC
HERO ID
62951
Reference Type
Journal Article
Year
1977
Language
English
PMID
| HERO ID | 62951 |
|---|---|
| In Press | No |
| Year | 1977 |
| Title | Metabolism in vivo of dioxane: Effect of inducers and inhibitors of hepatic mixed-function oxidases |
| Authors | Woo, YT; Argus, MF; Arcos, JC |
| Journal | Biochemical Pharmacology |
| Volume | 26 |
| Issue | 16 |
| Page Numbers | 1539-1542 |
| Abstract | In the preceding communication (I), we summarized our studies on the metabolism in vivo of dioxane which identified p-dioxane-2-one to be the major urinary metabolite. It is well documented that the activity of mixed-function oxidases (MFO) metabolizing foreign compounds can be modulated by various inducers, repressors and inhibitors (2-4). In order to investigate the involvement of MFO in the metabolism in vivo of dioxane, the effect of several such agents on the excretion of E-dioxane-2-one was studied. Male Sprague-Dawley rats (95-130 g) were used throughout. Three typical inducers of MFO were employed: phenobarbital (PB), the polychlorinated biphenyls, Aroclor 1254 (PCB) (Monsanto Chemical Co.), and 3-methylcholanthrene (MC). PB was dissolved in 0. 9% saline and administered i.p. at a dose of 80 mg/kg daily for 4 consecutive days prior to dioxane administration. PCB and MC were dissolved in corn oil; PCB was given at a single dose of 500 mg/kg 4 days prior to dioxane administration and MC at 40 mg/kg 24 hr prior to dioxane administration. Control rats received equivalent amounts of saline or corn oil. To repress the synthesis of cytochrome P-450 (5), cobaltous chloride (60 mg/kg) was injected s. c. 24 hr prior to dioxane administration. Dioxane (3 g/kg) was given i. p. and urine samples were collected at 8- or 12-hr intervals andtreated as previously (1). 2,4-Dichloro-6-phenylphenoxy ethylamine (DPEA), a potent, long-acting inhibitor of MFO (6, 7) (gift of Dr. R. E. McMahon. Eli Lilly Co. ), was dissolved in saline and given at the dose of 15. 9 mglkg 30 min prior to dioxane administration and 8, 16 and 24 hr thereafter. The amount of p-dioxane-2-one present in urine was determined by analytical gas chromatography using purified synthetic reference compound as standard. |
| Doi | 10.1016/0006-2952(77)90431-2 |
| Pmid | 901573 |
| Wosid | WOS:A1977DP40800017 |
| Url | https://linkinghub.elsevier.com/retrieve/pii/0006295277904312 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Aroclors; Dioxanes; Dioxins; Ethylamines; Methylcholanthrene; 56-49-5; Mixed Function Oxygenases; Oxidoreductases; Phenobarbital; YQE403BP4D; Index Medicus; Animals; Time Factors; Ethylamines -- pharmacology; Phenobarbital -- pharmacology; Aroclors -- pharmacology; Methylcholanthrene -- pharmacology; Enzyme Induction -- drug effects; Dioxanes -- metabolism; Mixed Function Oxygenases -- antagonists & inhibitors; Dioxanes -- urine; Liver -- drug effects; Liver -- enzymology; Dioxins -- metabolism; Oxidoreductases -- metabolism; Mixed Function Oxygenases -- metabolism; Mixed Function Oxygenases -- biosynthesis |
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