Impact of six fruits-banana, guava, mangosteen, pineapple, ripe mango and ripe papaya-on murine hepatic cytochrome P450 activities
ABSTRACT The effects of six Thai fruits, namely banana, guava, mangosteen, pineapple, ripe mango and ripe papaya, on cytochrome P450 (P450) activities were investigated. The median inhibitory concentrations (IC(50) ) of each of the fruit juices on CYP1A1, CYP1A2, CYP2E1 and CYP3A11 activities were determined. Pineapple juice showed the strongest inhibitory effect against all the evaluated P450 isozyme activities in mouse hepatic microsomes, followed by mangosteen, guava, ripe mango, ripe papaya and banana. The study was further performed in male ICR mice given pineapple juice intragastrically at doses of 10, 20 and 40 mg kg(-1) per day for 7 or 28 days. In a concentration-dependent fashion, the pineapple juice raised ethoxyresorufin O-deethylase, aniline hydroxylase and erythromycin N-demethylase activities, which are marker enzymatic reactions responsible for CYP1A1, CYP2E1 and CYP3A11, respectively. The effect of pineapple juice on the expression of CYP1A1, CYP2E1 and CYP3A11 mRNAs corresponded to their enzymatic activities. However, the pineapple juice significantly decreased methoxyresorufin O-demethylase activity. These observations supported that the six Thai fruits were a feasible cause of food-drug interaction or adverse drug effects owing to their potential to modify several essential P450 activities. Individuals consuming large quantities of pineapple for long periods of time should be cautioned of these potential adverse effects. Copyright © 2012 John Wiley & Sons, Ltd.
- SourceAvailable from: Nobuo Nemoto[Show abstract] [Hide abstract]
ABSTRACT: Expression of Cyp1a1 and Cyp1a2 genes was investigated in adult C57BL/6NCrj mouse hepatocytes in primary culture for up to 5 days. When the cells were cultivated as monolayers on collagen-coated dishes, CYP1A1 mRNA species were prominently induced after treatment with 3-methylcholanthrene (MCA) throughout the observation period. Substantial induction of CYP1A2 mRNA by MCA was also observed at day 1 of cultivation, followed by a decrease to very low levels thereafter. In contrast, when cultivated on non-coated dishes, the hepatocytes formed multicellular aggregates (spheroids) and prominent induction of both mRNA species was found for up to 5 days. Constitutive expression of CYP1A2 mRNA in spheroid culture was maintained throughout the observation period, whereas that in monolayer culture decreased rapidly. The time-course of the induced CYP1A2 mRNA amounts after the treatment with MCA or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) followed the same pattern as that of CYP1A1 mRNA. Expressed amounts of CYP1A1 or CYP1A2 mRNA in spheroid culture were higher than or similar to the levels in the case of in vivo production, respectively. Induction of both mRNA species was also observed in hepatocytes from nonresponsive DBA/2NCrj mouse in spheroid culture, but the expressed amount after MCA treatment was far smaller than for C57BL/6NCrj cells, despite equivalent expression in the two strains after TCDD. Activities of aryl hydrocarbon hydroxylase (AHH) and acetanilide 4-hydroxylase (AAH) were elevated with either type of cultivation after treatment with MCA or TCDD. Ratios of AAH to AHH were not changed between the two cultures after 24 h treatment. However, the ratios in spheroid culture after 48 h treatment increased, whereas they did not change in monolayer culture. The present observations indicate that the spheroid culture is more suitable than the monolayer system for studying the mechanism of Cyp1a2 gene expression in adult mouse hepatocytes.Japanese journal of cancer research: Gann 04/1993; 84(3):272-8. DOI:10.1111/j.1349-7006.1993.tb02867.x
- Science 10/1939; 90(2335):299. DOI:10.1126/science.90.2335.299 · 31.48 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great.Proceedings of the National Academy of Sciences 10/1993; 90(17):7915-22. DOI:10.1073/pnas.90.17.7915 · 9.81 Impact Factor