0000000000242854
AUTHOR
M. Suschetet
Inhibition of ethoxyresorufin deethylase activity by natural flavonoids in human and rat liver microsomes
Several flavones and flavonols (chrysin, quercetin, luteolin, flavone and 7, 8-benzoflavone) were found to inhibit ethoxyresorufin deethylase (EROD) activity in human and rat liver microsomes. In man, molecules without hydroxyl groups are more powerful inhibitors than polyhydroxylated flavonoids (7, 8-benzoflavone greater than flavone greater than chrysin greater than luteolin greater than quercetin greater than morin). In rat, chrysin was the strongest inhibitor and the less effective were morin and 7,8-benzoflavone. For all molecules human microsomes were more sensitive than rat microsomes. The most important difference concerned 7,8-benzoflavone which was 10,000-fold more potent in man.
Differential Effects of Nonhydroxylated Flavonoids as Inducers of Cytochrome P450 1A and 2B Isozymes in Rat Liver
Flavanone, flavone, and tangeretin differentially affected the activities of cytochrome P540 1A and 2B isozymes in rat liver. Flavone and, to a lesser extent, tangeretin, increased activities of ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and pentoxyresorufin O-dealkylase (PROD), whereas flavanone mainly enhanced PROD activity. Immunoblot analysis indicated that flavone and tangeretin increased cytochrome P450 1A1, 1A2, and 2B1,2 forms, whereas flavanone only enhanced the cytochrome P450 2B isozymes. Northern blot study showed that flavone and tangeretin increased the level of the cytochrome P450 1A2 mRNAs. The concentration of the other mRNAs were slightly or not affected…
Modulation of aflatoxin B1 carcinogenicity, genotoxicity and metabolism in rat liver by dietary carotenoids: evidence for a protective effect of CYP1A inducers
The effects of several carotenoids of vitamin A and of 3-methylcholanthrene have been tested on the initiation of hepatocarcinogenesis by aflatoxin B1, using the sequential protocol of Solt and Farber. AFB1-induced DNA single-strand breaks and AFB1-metabolism were also assessed. The P4501A inducer carotenoids (canthaxanthin, astaxanthin, beta-apo-8'-carotenal) and 3-methylcholanthrene reduce the carcinogenicity of AFB1, divert AFB1-metabolism into the less genotoxic aflatoxin M1 and reduce AFB1-induced DNA single-strand breaks: we conclude that these carotenoids exert their protective effect through the deviation of AFB1 metabolism towards detoxification pathways. beta-Carotene decreased AF…
Antimutagenic activity of organosulfur compounds from Allium is associated with phase II enzyme induction
In a previous study, we showed that naturally occurring organosulfur compounds (OSCs) from garlic and onion modulated the activation of carcinogen via the alteration of cytochromes P450. The present study was undertaken to determine the incidence of the in vivo induction of phase II enzymes by individual OSCs on the genotoxicity of several carcinogens. Diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered by gavage (1mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects of treatments on phase II enzymes and on the genotoxicity of carcinogens were evaluated with hepatic cytosols and microsomes from OSCs-treated…
Liver subcellular fractions from rats treated by organosulfur compounds from Allium modulate mutagen activation
The effects of in vivo administration of naturally occurring organosulfur compounds (OSCs) from Allium species were studied on the activation of several mutagens. Male SPF Wistar rats were given p.o. one of either diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) or dipropyl disulfide (DPDS) during 4 consecutive days and the ability of hepatic S9 and microsomes from treated rats to activate benzo[a]pyrene (BaP), cyclophosphamide (CP), dimethylnitrosamine (DMN), N-nitrosopiperidine (N-PiP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was determined in the Ames test. Administration of DAS, DPS and DPDS resulted in a significant increase of the activation of…
Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rat: Role of the modulation of aflatoxin B1 metabolism
To study the effects of carotenoids on the initiation of liver carcinogenesis by aflatoxin B1 (AFB1), male weanling rats were fed beta-carotene, beta-apo-8'-carotenal, canthaxanthin, astaxanthin or lycopene (300 mg/kg diet), or an excess of vitamin A (21000 RE/kg diet), or were injected i.p. with 3-methylcholanthrene (3-MC) (6 x 20 mg/kg body wt) before and during i.p. treatment with AFB1 (2 x 1 mg/kg body wt). The rats were later submitted to 2-acetylaminofluorene treatment and partial hepatectomy, and placental glutathione S-transferase-positive liver foci were detected and quantified. The in vivo effects of carotenoids or of 3-MC on AFB1-induced liver DNA damage were evaluated using diff…
In vivo antigenotoxic effects of dietary allyl sulfides in the rat
The effects of dietary administration of diallyl sulfide (DAS), diallyl disulfide (DADS) and allyl mercaptan (AM) on the genotoxicity of different chemicals were studied in two experimental systems: (i) measurement of hepatic DNA single-strand breaks induced in rats by aflatoxin B1 (AFB1), N-nitrosodimethylamine (NDMA) or methylnitrosourea (MNU); (ii) mutagenicity of AFB1 or NDMA on Salmonella typhimurium TA100 using hepatic S9 from rats fed allyl sulfides as the activation system. All compounds strongly reduced hepatic DNA breaks induced by AFB1 and NDMA but did not modify the genotoxicity of MNU. In the Ames test, the mutagenicity of NDMA was strongly inhibited by hepatic S9 from rats fed…
Dietary lycopene decreases the initiation of liver preneoplastic foci by diethylnitrosamine in the rat
To test whether carotenoids can modulate the initiation of liver preneoplasia by diethylnitrosamine (DEN) or by 2-nitropropane (2-NP) in a sequential protocol of hepatocarcinogenesis, male weanling rats were fed for three or four weeks (respectively) diets containing beta-carotene, canthaxanthin, astaxanthin, or lycopene (300 mg/kg diet) or an excess of vitamin A (15,000 retinol equivalents/kg diet) or were treated intraperitoneally with 3-methylcholanthrene. During this period, all rats were injected intraperitoneally with the initiator carcinogen, either 2-NP (6 times at 100 mg/kg body wt) or DEN (once at 100 mg/kg body wt). Three weeks after the termination of carotenoid or vitamin A fee…
Post-initiation modulating effects of allyl sulfides in rat hepatocarcinogenesis
Effects of administration of diallyl sulfide (DAS) and diallyl disulfide (DADS) on the promotion stage of hepatocarcinogenesis were investigated in rats using the Ito model. They were compared with those of phenobarbital (PB), a well-known liver promoter in rats. Initiation was induced by a single dose of N-nitrosodiethylamine (NDEA) and 3 weeks later, a partial hepatectomy was conducted. Two weeks after the NDEA injection, rats received either 0.05% allyl sulfides, PB or both in their diet for 8 weeks. Feeding with DAS increased the number of liver preneoplastic foci by 63% with respect to the untreated group. However, rats fed DAS showed a lower foci development than rats fed PB. The DADS…
Mechanisms involved in the chemoprevention of flavonoids
Flavonoids, widespread in edible plants, have been studied extensively for their anticarcinogenic properties. However, only few studies have been done with these constituents being administered by the dietary route. In our research, the effects of feeding rats with flavone, flavanone, tangeretin, and quercetin were investigated on two steps of aflatoxin B1 (AFB1)-induced hepatocarcinogenesis (initiation and promotion). Nonpolar flavonoids such as flavone, flavanone and tangeretin administered through the initiation period, decreased the number of -gamma-glutamyl transpeptidase-preneoplastic foci. In the same conditions of administration, quercetin, a polyhydroxylated flavonoid, showed no pr…
Flavonoids of honey and propolis : characterization and effects on hepatic drug-metabolizing enzymes and benzo(a)pyrene-DNA binding in rats
The influence of dietary sunflower honey, propolis, and a flavonoid extract of propolis was examined on drug-metabolizing enzyme activities in rat liver and on microsome-mediated binding of benzo[a]pyrene to DNA. Characterization of flavonoids present in sunflower honey and propolis was achieved in order to assess the relative effects of different components of honey and propolis. Honey and propolis contained the same major flavonoids, pinocembrin, chrysin, galangin, and pinobanksin. The concentration of flavonoids was higher in propolis. Sunflower honey produced no significant changes on phase I and phase II enzyme activities and no modification of in vitro binding of benzo[a]pyrene to DNA…