Metabolism of some naturally occurring isothiocyanates in the rat

Mennicke, W. H.; Görler, K.; Krumbiegel, Günter

doi:10.3109/00498258309052256

Cited by 97 publications

(61 citation statements)

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“…Following their absorption into the intestinal epithelium isothiocyanates are released into the systemic circulation and metabolized by the mercapturic acid (MA) pathway in the liver. Isothiocyanates initially form conjugates with glutathione, then undergo enzymic modification and are excreted in urine as their corresponding N-acetylcysteine conjugates or MA (Brüsewitz et al 1977;Mennicke et al 1983). Urinary isothiocyanate MA excretion therefore partially reflects isothiocyanate absorption in vivo, although variation in pre-and postabsorptive recovery may also be important.…”

Section: Digestive and Post-absorptive Fate Of Glucosinolates After Imentioning

confidence: 99%

“…An understanding of the digestive and absorptive fate of dietary glucosinolates and their isothiocyanate metabolites has emerged mostly from mechanistic studies in animal models such as rats and hamsters (Brüsewitz et al 1977;Mennicke et al 1983;Michaelsen et al 1994;Duncan et al 1997;Elfoul et al 2001). The low recoveries of intact glucosinolates and their metabolites in faeces of animals fed glucosinolates or isothiocyanates suggest that a substantial proportion of ingested glucosinolates and isothiocyanates are metabolised in vivo (Slominski et al 1988;Bollard et al 1997;Rouzaud et al 2003).…”

Section: Digestive and Post-absorptive Fate Of Glucosinolates After Imentioning

confidence: 99%

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Effect of cooking brassica vegetables on the subsequent hydrolysis and metabolic fate of glucosinolates

Rungapamestry

Duncan²,

Fuller³

et al. 2007

Proc. Nutr. Soc.

137

102

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The protective effects of brassica vegetables against cancer may be partly related to their glucosinolate content. Glucosinolates are hydrolysed by plant myrosinase following damage of plant tissue. Isothiocyanates are one of the main groups of metabolites of glucosinolates and are implicated in the preventive effect against cancer. During cooking of brassica the glucosinolate–myrosinase system may be modified as a result of inactivation of plant myrosinase, loss of enzymic cofactors such as epithiospecifier protein, thermal breakdown and/or leaching of glucosinolates and their metabolites or volatilisation of metabolites. Cooking brassica affects the site of release of breakdown products of glucosinolates, which is the upper gastrointestinal tract following consumption of raw brassica containing active plant myrosinase. After consumption of cooked brassica devoid of plant myrosinase glucosinolates are hydrolysed in the colon under the action of the resident microflora. Feeding trials with human subjects have shown that hydrolysis of glucosinolates and absorption of isothiocyanates are greater following ingestion of raw brassica with active plant myrosinase than after consumption of the cooked plant with denatured myrosinase. The digestive fate of glucosinolates may be further influenced by the extent of cell rupture during ingestion, gastrointestinal transit time, meal composition, individual genotype and differences in colonic microflora. These sources of variation may partly explain the weak epidemiological evidence relating consumption of brassica to prevention against cancer. An understanding of the biochemical changes occurring during cooking and ingestion of brassica may help in the design of more robust epidemiological studies to better evaluate the protective effects of brassica against cancer.

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Section: Digestive and Post-absorptive Fate Of Glucosinolates After Imentioning

confidence: 99%

Section: Digestive and Post-absorptive Fate Of Glucosinolates After Imentioning

confidence: 99%

Effect of cooking brassica vegetables on the subsequent hydrolysis and metabolic fate of glucosinolates

Rungapamestry

Duncan²,

Fuller³

et al. 2007

Proc. Nutr. Soc.

137

102

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show abstract

“…Four ml urine/duplicate were analyzed. NAcetyl-S-(N-butylthiocarbamoyl)-L-cysteine was synthesized as its dicyclohexylamine salt (19) and used as an internal standard. N-Acetyl-S-(N-allylthiocarbamoyl)-L-cysteine and Nacetyl-S-(N-phenethylthiocarbamoyl)-L-cysteine, which are the mercapturic acids of allyl isothiocyanate and phenethyl isothiocyanate, respectively, were synthesized as their dicyclohexylamine salts for determination of response factors.…”

Section: Chemical Analysismentioning

confidence: 99%

Hydrolysis of Glucosinolates to Isothiocyanates after Ingestion of Raw or Microwaved Cabbage by Human Volunteers

Rouzaud¹,

Young²,

Duncan³

2004

Cancer Epidemiology, Biomarkers &Amp; Prevention

127

109

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Cabbage contains the glucosinolate sinigrin, which is hydrolyzed by myrosinase to allyl isothiocyanate. Isothiocyanates are thought to inhibit the development of cancer cells by a number of mechanisms. The effect of cooking cabbage on isothiocyanate production from glucosinolates during and after their ingestion was examined in human subjects. Each of 12 healthy human volunteers consumed three meals, at 48-h intervals, containing either raw cabbage, cooked cabbage, or mustard according to a cross-over design. At each meal, watercress juice, which is rich in phenethyl isothiocyanate, was also consumed to allow individual and temporal variation in postabsorptive isothiocyanate recovery to be measured. Volunteers recorded the time and volume of each urination for 24 h after each meal. Samples of each urination were analyzed for N-acetyl cysteine conjugates of isothiocyanates as a measure of entry of isothiocyanates into the peripheral circulation. Excretion of isothiocyanates was rapid and substantial after ingestion of mustard, a source of preformed allyl isothiocyanate. After raw cabbage consumption, allyl isothiocyanate was again rapidly excreted, although to a lesser extent than when mustard was consumed. On the cooked cabbage treatment, excretion of allyl isothiocyanate was considerably less than for raw cabbage, and the excretion was delayed. The results indicate that isothiocyanate production is more extensive after consumption of raw vegetables but that isothiocyanates still arise, albeit to a lesser degree, when cooked vegetables are consumed. The lag in excretion on the cooked cabbage treatment suggests that the colon microflora catalyze glucosinolate hydrolysis in this case.

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“…It is striking that the ability of these compounds to form GSH conjugates also required the presence of an a-hydrogen (34,35).…”

mentioning

confidence: 99%

“…Quinones are good Michael acceptors and their reaction with GSH is enzyme promoted. Some organic isothiocyanates are metabolized to products that suggest an initial conjugation with GSH (34,35), and some thiocarbamates appear also to undergo initial sulfoxidation followed by conjugation with GSH (30).…”

mentioning

confidence: 99%

Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis.

Talalay

Long

Prochaska

1988

Proc. Natl. Acad. Sci. U.S.A.

520

325

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Carcinogenesis is blocked by an extraordi- Although bifunctional inducers appear to elevate phase II enzymes in part by binding to the Ah (aryl hydrocarbon) receptor, the molecular mechanisms by which monofunctional inducers act are less clear (3). This paper extends our earlier efforts to identify structural features important for phase II enzyme induction by diphenols and phenylenediamines (5). Since the specific activity of QR in the Hepa lclc7 murine hepatoma cells is raised by virtually all compounds that produce coordinate elevations of phase II enzymes in vivo (4, 5, 7), this system was used to determine the potency of various types of enzyme inducers. Some inducers identified in cell culture were also tested as inducers of QR and GST in mouse tissues.We report here that phase II enzyme inducers contain, or acquire by metabolism, a hitherto unrecognized and distinctive chemical and structural feature-i.e., an electrophilic olefin or related electron-deficient center. They are, therefore, Michael reaction acceptors.t This generalization has led to the identification of a number of phase II enzyme inducers that are Michael acceptors and are potential chemoprotectors. Most inducers are also substrates for GST, but whether this merely reflects their electrophilic nature or is an intrinsic aspect of the mechanism of induction is unclear.MATERIALS AND METHODS QR activities of Hepa lclc7 murine hepatoma cells were measured in cells grown in microtiter plates (8). The potency of compounds was determined from plots relating the ratio of treated to basal (vehicle only) of specific activities of QR to the concentration of inducer. Potencies are expressed as the concentrations required to double (designated CD) the basal specific activity of QR. Induction of cytosolic QR and GST activities in female CD1 mouse tissues was assessed by a standard protocol (9, 10). All compounds were of the highest quality obtainable commercially and were purified when necessary.Abbreviations: QR, quinone reductase; GSH, glutathione; GST, glutathione S-transferase; CD, concentration of a compound that doubles the specific activity of QR; BHA, 2(3)-tert-butyl-4-hydroxyanisole; CDNB, 1-chloro-2,4-dinitrobenzene; DCNB, 1,2-dichloro4nitrobenzene. *Enzymes of xenobiotic metabolism are of two types: (i) phase I enzymes (e.g., cytochromes P450) functionalize compounds usually by oxidation or reduction; and (ii) phase II enzymes conjugate functionalized compounds with endogenous ligands (e.g., glutathione, glucuronic acid). Quinone reductase may be considered a phase II enzyme since it does not introduce new functional groups, is often induced coordinately with other phase II enzymes, and protects cells against toxic agents. tIn 1887 A. Michael reported that olefins conjugated with electronwithdrawing groups (Z) are susceptible to attack by nucleophiles. These so-called "Michael acceptors" have the structures CH2=CH-Z, Z'-CH=CH-Z (including quinones), or R-CLC-Z (acetylenes). The or4er of reactivity of CH2=CH-Z with morpholine or pyrroli...

show abstract

Metabolism of some naturally occurring isothiocyanates in the rat

Cited by 97 publications

References 4 publications

Effect of cooking brassica vegetables on the subsequent hydrolysis and metabolic fate of glucosinolates

Effect of cooking brassica vegetables on the subsequent hydrolysis and metabolic fate of glucosinolates

Hydrolysis of Glucosinolates to Isothiocyanates after Ingestion of Raw or Microwaved Cabbage by Human Volunteers

Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis.

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