Reference

Inhibition of aflatoxin B1 carcinogenesis in rainbow trout by flavone and indole compounds

Inhibition of aflatoxin B1 carcinogenesis in rainbow trout by flavone and indole compounds. Nixon, Joseph E.; Hendricks, Jerry D.; Pawlowski, Norman E.; Pereira, Cliff B.; Sinnhuber, Russell O.; Bailey, George S. (Dep. Food Sci. Technol., Oregon State Univ., Corvallis, OR 97331, USA). Carcinogenesis (London), 5(5), 615-19 (English) 1984. CODEN: CRNGDP. ISSN: 0143-3334. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Section cross-reference(s): 1, 17 The following compds.: 50 and 500 ppm b-naphthoflavone (BNF) [6051-87-2], 1000 ppm flavone [525-82-6], 1000 ppm of a tangeretin [481-53-8] nobiletin [478-01-3] mixt., 1000 ppm b-ionone [79-77-6], 1000 ppm indole-3-carbinol (I3C) [700-06-1] and 2000 ppm quercetin [117-39-5] were examd. for protection against aflatoxin B1 (AFB1)(I) [1162-65-8] hepatocarcinogenesis, induction of the mixed-function oxidase (MFO) [9040-60-2] system and metab. of AFB1 in rainbow trout (Salmo gairdneri). These compds. were fed to fingerling rainbow trout for 8 wk. At that time the activity of several MFO enzymes and cytochrome P 450 [9035-51-2] content were measured and the trout were exposed for 2 wk to 20 ppb AFB1 in the same diets. After feeding the test diets without AFB1 for another 6 wk and basal diet for another 52 wk, the tumor incidence was detd. The effect of BNF and I3C on in vivo binding of AFB1 to DNA was also measured in sep. groups of trout. BNF induced the trout MFO system in a dose-dependent manner, tangeretin-nobiletin was less effective, and I3C did not induce. BNF showed significant alterations in the metab. of AFB1 to aflatoxicol [29611-03-8] and aflatoxin M1 [6795-23-9] using cell fractions from pretreated fish. None of the other compds., including I3C showed such an effect. Despite the apparent lack of in vitro effect of I3C, both BNF and I3C reduced AFB1-DNA binding in vivo. I3C and BNF provided marked protection against AFB1-induced hepatocarcinogenesis, whereas the other compds. were less effective. The 58 wk tumor incidences were 4% for I3C, 6% for BNF, and 18% for BNF, compared to 38% for the AFB1-pos. control. These data demonstrate that gross induction of the MFO system was not necessarily required for alterations in DNA adduct formation in vivo or protection against AFB1 carcinogenesis. Both BNF and I3C provided marked protection but only BNF induced the MFO system.

In vitro and in vivo activation of oxidative drug metabolism by flavonoids

In vitro and in vivo activation of oxidative drug metabolism by flavonoids. Lasker, Jerome M.; Huang, Moutuan; Conney, Allan H. (Dep. Biochem. Drug Metab., Hoffmann-La Roche Inc., Nutley, NJ 07110, USA). J. Pharmacol. Exp. Ther., 229(1), 162-70 (English) 1984. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 18 The effect of several naturally occurring and synthetic flavonoids on the metab. of zoxazolamine [61-80-3] to 6-hydroxyzoxazolamine [1750-46-5] was studied. Flavone [525-82-6], nobiletin [478-01-3], tangeretin [481-53-8] and 7,8-benzoflavone [604-59-1] (50-250 mM) stimulated the metab. of zoxazolamine by liver microsomes obtained from 5-day-old rats. Evidence was obtained indicating that flavone changed the apparent Km and Vmax values for zoxazolamine hydroxylation. The i.p. administration of 5 mmol of flavone, nobiletin, tangeretin, or 7,8-benzoflavone concurrently with 740 nmol of zoxazolamine immediately stimulated the total body metab. of zoxazolamine to 6-hydroxyzoxazolamine. The magnitude of the flavone-mediated increases in n zoxazolamine hydroxylation in vivo was dependent on the dose of flavone and the dose of zoxazolamine administered. The i.p. administration of 5 mmol of flavone caused a 3- to 5-fold stimulation in the in vivo metab. of 740 to 3000 nmol of zoxazolamine, but flavone had little or no stimulatory effect when 74 nmol of zoxazolamine was adminstered. Flavone stimulated zoxazolamine metab. both in vitro and in vivo in control or phenobarbital-treated rats, but flavone inhibited the in vitro and in vivo hydroxylation of zoxazolamine when rats induced with 5,6-benzoflavone [6051-87-2] were studied. Although flavone activated zoxazolamine metab. in vivo in neonatal rats, it did not activate the in vivo metab. of benzo(a)pyrene. The in vitro addn. of the hydroxylated flavonoids apigenin [520-36-5], chrysin [480-40-0], fisetin [528-48-3], morin [480-16-0], and quercetin [117-39-5] inhibited the hydroxylation of zoxazolamine by liver microsomes from neonatal rats, but studies with quercetin and apigenin indicated that these flavonoids had no effect on the in vivo metab. of zoxazolamine.