Dietary effects on drug metabolism by the mixed-function oxidase system

Yang, Chung S.; Yoo, Jeong-Sook H.

doi:10.1016/0163-7258(88)90102-7

Cited by 50 publications

(6 citation statements)

References 109 publications

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“…Dietary fish oil induces certain forms of microsomal cytochrome P450 but leaves others unaffected (28)(29)(30)(31). The effect of fish oil diets on cytochrome P4501A2, the isozyme catalyzing the formation of N-OH-IQ from IQ (6), is not known, nor are its effects on esterification enzymes or on other P450 isozymes that may be involved in the detoxification of IQ.…”

Section: Resultsmentioning

confidence: 99%

Dietary modulation of DNA adduct formation of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in the male Fischer 344 rat.

Schut

1994

Environ Health Perspect

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In numerous in vivo systems it has been shown that diets high in menhaden oil (a fish oil high in .-3 fatty acids) can inhibit the carcinogenic process. In the present study, we have assessed the effects of a diet containing menhaden oil on 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA adduct formation in target tissues of the male Fischer 344 rat. Young adult male Fischer 344 rats were maintained on either a) an AIN-76A diet containing 5% corn oil, b) an isocaloric AIN-76A diet modified to contain 2% corn oil and 19% menhaden oil (MO diet), or c) a regular laboratory rodent diet (chow diet) for 6 weeks prior to receiving a single oral dose of 10 or 50 mg IQ/kg. Groups of four animals were killed 1 or 6 days after IQ administration. Using 32P-postlabeling assays, IQ-DNA adducts were isolated and quantitated in the liver, small intestine, and large intestine. Adduct patterns were similar in all cases. Adduct levels, expressed as relative adduct labeling values (RAL x 107), were related to dose in all three tissues, with liver levels up to 1 0-fold higher than the large intestine and up to 20-fold higher than the small intestine. On day one, liver adduct levels in animals on the AIN-76A diet were similar to those in animals on the chow diet, but those in animals on the MO diet were approximately 2-fold lower. On day six, these differences were much lower, probably as a result of the more efficient removal of liver adducts in animals on AIN-76A or chow diets. In the intestines, removal of adducts in animals on either AIN-76A or MO diet was slower than that in the liver, while that in animals on the chow diet was similar to that in the liver. While dietary MO is generally thought to inhibit experimental tumorigenesis at the promotional stage, the present results show that MO diets may also inhibit the initiation process by inhibiting the initial rate of IQ-DNA adduct formation. It also appears, however, that MO diets may impair the process of adduct removal. -Environ Health Perspect 1 02 (Suppl 6:57-60 (1994)

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Section: Resultsmentioning

confidence: 99%

Dietary modulation of DNA adduct formation of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in the male Fischer 344 rat.

Schut

1994

Environ Health Perspect

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“…In the past 10 years, increased numbers of specific isozyme forms of this cytochrome P450 system were identified (Nebert et al 1989). Quantitative and qualitative characterization, of the various isozymes of the cytochrome P-450 superfamily by genetic code, gene location, immunological properties, spectral characteristics and substrate selective metabolism is considered an important aspect of toxicological and pharmacological studies (Bostick et al 1981;Ioannides et al 1984;Burke et al 1985;McDanell et al 1987;Yang and Yoo 1988;Nebert et al 1989). Direct measurement of the O-dealkylation activities of the substrates ER and PR has become a sensitive and highly selective characteristic for induction of cytochrome P-450 isozymes IA1 by 3-methylcholanthrene (3-MC) and IIB 1 by phenobarbital (PB) Mayer 1974, 1975;Burke et al 1977;Lubet et al 1985).…”

Section: Introductionmentioning

confidence: 99%

Interlaboratory comparison of microsomal ethoxyresorufin and pentoxyresorufin O-dealkylation determinations: standardization of assay conditions

et al. 1992

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Assay conditions and results of cytochrome P-450 dependent 7-ethoxyresorufin (ER) and 7-pentoxyresorufin (PR) O-dealkylation (OD) by rat liver microsomes were compared by four laboratories in the Netherlands. Microsomal mixtures were prepared from control, 3-methylcholanthrene and phenobarbital pretreated animals, resulting in different levels of cytochrome P-450 isozymes. EROD and PROD activities were determined in each laboratory according to their own protocols. Considerable variability was found both between and within laboratories. Further studies demonstrated that protocol differences are important factors causing this interlaboratory variation. Main factors of influence were buffer type, batch of resorufin used for calibration, substrate solvent and substrate concentration. Based on the results obtained, standardized protocols for optimized measurement of microsomal EROD and PROD activities were developed. Additional experiments demonstrated that the use of these standardized protocols reduced intralaboratory variation in both the EROD and the PROD assay, whereas it also reduced the interlaboratory variability for the PROD determinations. The interlaboratory variation for measurement of microsomal EROD activities was only reduced for the laboratories using a Cobas-Bio analyzer. The results of the present study demonstrate clearly that data obtained with EROD and PROD activity measurements are highly sensitive to factors frequently varying from one laboratory to another. In addition, they demonstrate the necessity to be careful with absolute values presented in the literature for these activities, unless well characterized assay conditions are applied.

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“…As a consequence of this chemical change, dynamic properties of membranes such as fluidity, permeability and compressibility may be modified [2], affecting various biological functions, including the activity of enzymatic systems involved in the metabolism of endogenous substances and xenobiotics [3]. The activity of many integral membrane proteins, such as the cytochrome P450 (cyt P450) mixed function oxidases (MFOs) is highly dependent upon the lipid microenvironment, determined by the phospholipidic matrix and their fatty acid composition, the cholesterol content [4,5] and minor constituents such as vitamin E [6,7]. Many effects of different dietary fats on the hepatic metabolism of chemicals dependent on cyt P450 systems have been described since the early works of Wade and Norred [8].…”

Section: Introductionmentioning

confidence: 99%

Effect of Dietary Oils, Cholesterol and Antioxidant Vitamin Supplementation on Liver Microsomal Fluidity and Xenobiotic-Metabolizing Enzymes in Rats

Lutz

Bonilla²,

Concha³

et al. 1998

Ann Nutr Metab

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This study was undertaken to compare the effects of four oils: corn (C), olive (O), hazelnut (H) or fish (F), and the intake of two supplements: cholesterol, 1% (Ch) or dl-α-tocopherol acetate, 500 mg/kg, and β-carotene, 30 mg/kg (V), on liver microsomal fluidity, cyt P450 content and aniline hydroxylase (AH), aminopyrine-N-dimethylase (AND) and UDP-glucuronyltransferase (UDP-GT) activities. Male Sprague-Dawley rats (n = 6/group) were fed semipurified diets containing 15% oil, without or with Ch or V, for 20 days. Dietary intake and feed efficiency were lower in rats fed F. Relative liver weight was higher in animals fed F, similar in O and H, and lower in the group fed C. The intake of V increased feed intake in C+V group and decreased the relative liver weight of F+V group, which also decreased with the intake of F+Ch. Ch intake increased the relative liver weight in all groups consuming vegetable oils. Cyt P450 content was higher in rats fed F. Decreased cyt P450 content was observed in C+Ch and F+Ch groups, while it augmented in H+Ch group. Mixture V increased cyt P450 in rats fed C+V, F+V and O+V. The highest membrane fluidity was observed in rats fed F. Fluidity was also higher in group H versus O or C. The intake of Ch decreased microsomal fluidity in all groups, while V induced an increase in microsomal fluidity in group O+V. Rats fed F exhibited higher enzyme activities. AND activity increased with V only in rats fed H+V, while AH activity increased with V intake in groups F+V and O+V. In the C+V group, fluidity was not affected by V, while the cyt P450 content and UDP-GT activity increased. The O+V group exhibited lower UDP-GT activity and higher fluidity and cyt P450 content. The activity of AH decreased in groups F+Ch and C+Ch. UDP-GT activity was higher in rats fed F. It diminished after the intake of Ch in H+Ch and F+Ch. These results indicate that although AH and AND act in the same microsomal metabolic pathway, their localization into the membrane may be determinant of their activity and the response to dietary lipids. It is shown that F intake exerts the most significant effects upon liver microsomal properties, e.g. higher fluidity, cyt P450 content and enzymatic activities, an effect that prevails over the intake of the supplements tested.

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Dietary effects on drug metabolism by the mixed-function oxidase system

Cited by 50 publications

References 109 publications

Dietary modulation of DNA adduct formation of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in the male Fischer 344 rat.

Dietary modulation of DNA adduct formation of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in the male Fischer 344 rat.

Interlaboratory comparison of microsomal ethoxyresorufin and pentoxyresorufin O-dealkylation determinations: standardization of assay conditions

Effect of Dietary Oils, Cholesterol and Antioxidant Vitamin Supplementation on Liver Microsomal Fluidity and Xenobiotic-Metabolizing Enzymes in Rats

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