indole-3-acetonitrile and indole-3-carbinol

A systematic investigation was carried out on the influence of fermentation on glucosinolates and their degradation products from fresh raw cabbage, throughout fermentation at 20 °C and storage at 4 °C. Glucosinolates were degraded dramatically between Day 2 and 5 of fermentation and by Day 7 there was no detectable amount of glucosinolates left. Fermentation led to formation of potential bioactive compounds ascorbigen (13.0 μmol/100 g FW) and indole-3-carbinol (4.52 μmol/100g FW) with their higher concentrations from Day 5 to Day 9. However, during storage indole-3-carbinol slowly degraded to 0.68 μmol/100 g FW, while ascorbigen was relatively stable from Week 4 until Week 8 at 6.78 μmol/100 g FW. In contrast, the content of indole-3-acetonitrile decreased rapidly during fermentation from 3.6 to 0.14 μmol/100 g FW. The results imply a maximum of health beneficial compounds after fermentation (7-9 days) in contrast to raw cabbage or stored sauerkraut.

Topics: Brassica; Fermentation; Glucosinolates; Indoles

The aim of the study was to investigate the effect of storage on the contents of glucosinolates (GLS) and their degradation products in a boiled white cabbage. A 24h storage at 4 °C resulted in a decrease in GLS content (20-40%, depending on the cooking time applied) in the edible parts. The most significant losses were observed for sinigrin (20-45%), and the least for glucobrassicin (12-32%). Storage had a diversified effect on GLS breakdown products (indole-3-acetonitrile, indole-3-carbinol, ascorbigen and 3,3'-diindolylmethane released from glucobrassicin and 4-methylsulfinylbutanenitrile released from glucoiberin) in the boiled cabbage. The increase in the content of indole-3-acetonitrile, especially considerable within the first 24h of storage (and a simultaneous decrease in glucobrassicin) clearly indicates that degradation of GLS may occur during storage or cooling to 4 °C.

Topics: Ascorbic Acid; Brassica; Drug Stability; Fermentation; Food Handling; Food Preservation; Glucosinolates; Hot Temperature; Indoles

The mycotoxin fumonisin B1 (FB1) causes the accumulation of reactive oxygen species (ROS) which then leads to programmed cell death (PCD) in Arabidopsis. In the process of studying FB1-induced biosynthesis of glucosinolates, we found that indole glucosinolate (IGS) is involved in attenuating FB1-induced PCD. Treatment with FB1 elevates the expression of genes related to the biosynthesis of camalexin and IGS. Mutants deficient in aliphatic glucosinolate (AGS) or camalexin biosynthesis display similar lesions to Col-0 upon FB1 infiltration; however, the cyp79B2 cyp79B3 double mutant, which lacks induction of both IGS and camalexin, displays more severe lesions. Based on the fact that the classic myrosinase β-thioglucoside glucohydrolase (TGG)-deficient double mutant tgg1 tgg2, rather than atypical myrosinase-deficient mutant pen2-2, is more sensitive to FB1 than Col-0, and the elevated expression of TGG1, but not of PEN2, correlates with the decrease in IGS, we conclude that TGG-dependent IGS hydrolysis is involved in FB1-induced PCD. Indole-3-acetonitrile (IAN) and indole-3-carbinol (I3C), the common derivatives of IGS, were used in feeding experiments, and this rescued the severe cell death phenotype, which is associated with reduced accumulation of ROS as well as increased activity of antioxidant enzymes and ROS-scavenging ability. Despite the involvement of indole-3-acetic acid (IAA) in restricting FB1-induced PCD, feeding of IAN and I3C attenuated FB1-induced PCD in the IAA receptor mutant tir1-1 just as in Col-0. Taken together, our results indicate that TGG-catalyzed breakdown products of IGS decrease the accumulation of ROS by their antioxidant behavior, and attenuate FB1 induced PCD in an IAA-independent way.

Topics: Arabidopsis; Arabidopsis Proteins; Cell Death; Cytochrome P-450 Enzyme System; Fumonisins; Glucosinolates; Glycoside Hydrolases; Indoleacetic Acids; Indoles; Mutation; Thiazoles

The aim of the study was to investigate the effect of the pasteurization process on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. Pasteurization was run at a temperature of 80 °C for 5-30 min. Significant changes were only observed in contents of ascorbigen and 3,3'-diindolylmethane. The total content of the compounds analyzed in cabbage pasteurized for 10-30 min was found to be decreased by ca. 20%, and the losses were due to thermal degradation of the predominating ascorbigen. Pasteurization was found not to exert any considerable effect on contents of indole-3-acetonitrile and indole-3-carbinol in cabbage nor did it affect contents of the compounds analyzed in juice.

Topics: Ascorbic Acid; Brassica; Fermentation; Glucosinolates; Hot Temperature; Indoles; Pasteurization

The aim of the study was to investigate the effect of the boiling process on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. The cabbage was boiled for 5 to 60 min. Boiling resulted in a decrease of the total content of the compounds analysed. The changes were mainly caused by leaching of ascorbigen predominating in cabbage into cooking water and by its thermal hydrolysis. Ascorbigen losses resulting from thermal hydrolysis accounted for 30% after 10 min of boiling and for 90% after 60 min of boiling. One of the ascorbigen breakdown products was indole 3 carbinol; the decrease in ascorbigen content was accompanied by a drastic increase in the content of 3,3'-diindolylmethane, a condensation product of indole-3-carbinol. After 40 and 50 min of boiling, the total content of 3,3'-diindolylmethane in cabbage and cooking water was approximately 0.2 micromol/100 g and was 6-fold higher than that in uncooked cabbage. 3,3'-Diindolylmethane synthesis proceeded within the plant tissue. After 10 min of boiling, the content of free indole-3-carbinol and indole-3-acetonitrile stabilized at the level of about 80% as compared to the uncooked cabbage.

Topics: Anticarcinogenic Agents; Ascorbic Acid; Brassica; Fermentation; Food Handling; Hot Temperature; Indoles

In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague-Dawley rats. While treatment of rat liver slices for 72 hours with 2-200 microM of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 microM 3,3'-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears to be a mixed inducer of CYP in rat liver slices having effects on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases in liver slice reduced glutathione levels and glutathione S-transferase activity were also observed after DIM treatment. While aflatoxin B1 and monocrotaline produced a concentration-dependent inhibition of protein synthesis in 72-hour-cultured rat liver slices, cytotoxicity was markedly reduced in liver slices cultured with 50 microM DIM. These results demonstrate that cultured rat liver slices may be employed to evaluate the effects of chemicals derived from cruciferous and other vegetables on CYP isoforms. In addition, liver slices can also be utilized to examine the ability of such chemicals to modulate xenobiotic-induced toxicity.

Topics: Aflatoxin B1; Animals; Anticarcinogenic Agents; Carcinogenicity Tests; Carcinogens; Cytochrome P-450 Enzyme System; Drug Interactions; In Vitro Techniques; Indoles; Liver; Male; Monocrotaline; Rats; Rats, Sprague-Dawley; Xenobiotics

4-chloro-methoxyindole is a naturally occurring compound in Vicia faba which can easily react with nitrite to form a N-nitroso compound. In this in vitro study, the potential genotoxic effects of nitrosated 4-chloro-6-methoxyindole and its structural analogue 4-chloroindole were evaluated for the first time by using both Salmonella and Chinese hamster V79 cells. Additionally, the inhibition of gap junctional intercellular communication in V79 cells by these compounds was determined; this is a validated parameter for tumor-promoting activity. Most assays were also performed with nitrosated indole-3-acetonitrile, a naturally occurring compound in brassicas. Both nitrosated chloroindoles were highly mutagenic to Salmonella typhimurium TA100 without the need of exogenous metabolic activation and were potent inducers of Sister Chromatid Exchanges. Nitrosated indole-3-acetonitrile generated the same effects, although at much higher concentrations. Equivocal results were obtained for the nitrosated chloroindoles in a forward mutation assay using the hypoxanthine guaninephosphoribosyltransferase locus. All nitrosated indole compounds significantly inhibited gap junctional intercellular communication. These results indicate that nitrosated chloroindoles and nitrosated indole-3-acetonitrile should be considered as mutagens and agents with potential tumor-promoting capacity.

Topics: Animals; Carcinogenicity Tests; Carcinogens; Cell Communication; Cell Line; Cricetinae; Cricetulus; Indoles; Mutagenicity Tests; Mutagens; Mutation; Nitrosation; Salmonella typhimurium; Sister Chromatid Exchange

In this study we investigated the role of indole-3-acetonitrile, indole-3-carbinol, indole and tryptophan in the formation of N-nitroso compounds in green cabbage extracts. Green cabbage extracts were separated by gel permeation chromatography. Fractions were treated with nitrite, tested for mutagenicity and analysed for total N-nitroso content. Fractions in which spiked indole-3-acetonitrile, indole-3-carbinol, indole and tryptophan eluted appeared to be low in mutagenic activity and contained relatively small amounts of N-nitroso compounds. To detect indole compounds other than the ones used in the gel permeation chromatography experiments, high-performance liquid chromatography and gas chromatography-mass spectrometry analyses were performed of green cabbage extracts. Indole-3-carboxaldehyde was found to be the most commonly occurring indole compound, but it did not show direct mutagenic activity upon nitrite treatment. Indole-3-acetonitrile was the second most common compound; although it was mutagenic after nitrite treatment, its contribution to the mutagenicity of nitrite-treated green cabbage was roughly estimated to be only 2%. No other indole compounds were detected. From this study we conclude that neither the tested indole compounds nor indole-3-carboxaldehyde play a significant role in the formation of direct mutagenic N-nitroso compounds in nitrite-treated green cabbage extracts.

Topics: Brassica; Chromatography, Gel; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Glucosinolates; Indoles; Mutagens; Nitroso Compounds; Salmonella typhimurium; Tryptophan

Dietary indoles in cruciferous vegetables induce cytochrome P450 enzymes and have prevented tumors in various animal models. Because estradiol metabolism is also cytochrome P450 mediated and linked to breast cancer risk, indoles may similarly reduce estrogen-responsive tumors in humans. We examined several indoles in female Sprague-Dawley rats for induction of hepatic estradiol 2-hydroxylation. The most potent inducer, indole-3-carbinol, was administered to humans (500 mg daily for 1 wk). It significantly increased the extent (mean +/- SEM) of estradiol 2-hydroxylation from 29.3% +/- 2.1% to 45.6% +/- 2.1% (P less than .001). These results indicate that indole-3-carbinol strongly influences estradiol metabolism in humans and may provide a new chemopreventive approach to estrogen-dependent diseases.

Topics: Animals; Carboxylic Acids; Cytochrome P-450 Enzyme System; Diet; Estradiol; Humans; Hydroxylation; Indoles; Male; Mice; Mice, Inbred Strains

The nitrosation rates of indole-3-acetonitrile, indole-3-carbinol, indole and 4-chloroindole and the stability of their nitrosated products were investigated. Each of the nitrosated indole compounds was directly mutagenic to Salmonella typhimurium TA100 in the following order of potency: 4-chloroindole much greater than indole-3-carbinol greater than or equal to indole greater than indole-3-acetonitrile. Total N-nitroso determinations, carried out according to a modified method of Walters et al. (Analyst, Lond. 1978, 103, 1127), and Ames test results revealed that each of the indole compounds immediately formed mutagenic N-nitroso products upon nitrite treatment under acidic conditions. However, the nitrosation rates of indole and 4-chloroindole were higher than those of indole-3-acetonitrile and indole-3-carbinol. For indole-3-carbinol, indole-3-acetonitrile and indole, no change in the amount of nitrosated products was observed at increasing incubation times from about 15 up to 60 min. For 4-chloroindole the amount of nitrosated products decreased with increasing incubation times. In all cases the responses in the Ames test paralleled the amounts of nitrosated products. The stabilities of the nitrosated products of the indole compounds were investigated at pH 2 and 8. Both mutagenicity data and measurements by high-performance liquid chromatography using a photohydrolysis detector indicated that the nitrosation products of indole-3-acetonitrile, indole-3-carbinol and indole were more stable at pH 8 than at pH 2. Conversely, nitrosated 4-chloroindole was stable at pH 2 but not at pH 8. The pH 8 chromatograms showed a large nitrite peak. From this we hypothesized that the presence of free nitrite might be responsible for the stability of nitrosated indole-3-acetonitrile, indole-3-carbinol and indole at pH 8. Experiments confirmed the existence of an equilibrium between the nitrosated indole compound and the free indole compound plus nitrite.

Topics: Biotransformation; Chemical Phenomena; Chemistry; Chromatography, High Pressure Liquid; Hydrolysis; Indoles; Mutagenicity Tests; Nitrosation; Photochemistry; Salmonella typhimurium; Spectrophotometry, Ultraviolet

Topics: Animals; Aroclors; Benzoflavones; beta-Naphthoflavone; Chlorodiphenyl (54% Chlorine); Cytochrome P-450 Enzyme System; Enzyme Induction; Indoles; Male; Mice; Mice, Inbred Strains; Microsomes, Liver; Phenobarbital; Rabbits; Rats; Rats, Inbred Strains; Species Specificity

Indole-3-carbinol, 3,3'-diindolylmethane, and indole-3-acetonitrile, three indoles occurring in edible cruciferous vegetables, have been studied for their effects on 7,12-dimethylbenz(a)anthracene-induced mammary tumor formation in female Sprague-Dawley rats and on benzo(a)pyrene-induced neoplasia of the forestomach in female ICR/Ha mice. When given by p.o. intubation 20 hr prior to 7,12-dimethylbenz(a)anthracene administration, indole-3-carbinol and 3,3'-diindolylmethane had an inhibitory effect on mammary tumor formation, but indole-3-acetonitrile was inactive. Indole-3-carbinol when added to the diet for 8 days prior to challenge with 7,12-dimethylbenz(a)anthracene inhibited mammary tumor formation, whereas indole-3-acetonitrile did not. Dietary administration of all three indoles inhibited benzo(a)pyrene-induced neoplasia of the forestomach in ICR/Ha mice. The identification of dietary constituents that can inhibit chemical carcinogens ultimately may be of value in understanding the balance of factors that determines the neoplastic response to these cancer-producing agents in the environment.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Acetonitriles; Animals; Benz(a)Anthracenes; Diet; Female; Indoles; Mammary Neoplasms, Experimental; Mice; Mice, Inbred ICR; Neoplasms, Experimental; Rats; Stomach Neoplasms