Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Isothiocyanates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed2001

Analgesic activity and opioid receptor selectivity of stereoisomers of ohmefentanyl isothiocyanate.

Ohmefentanyl is a very potent and highly selective agonist for mu-opioid receptors. We now study analgesia, in vitro activity and opioid receptor affinity of the stereoisomers of ohmefentanyl isothiocyanate. We found that some isomers of ohmefentanyl isothiocyanate had a potent analgesic effect and that all isomers except (3R,4S,2'S)-ohmefentanyl isothiocyanate had a more potent inhibitory action on the electrically evoked contractions of mouse vas deferens than of guinea pig ileum. The inhibitory actions could be antagonized by naloxone. However, compared with the activity of the corresponding stereoisomers of ohmefentanyl, these ohmefentanyl isothiocyanates had significantly reduced analgesia and in vitro activity. They also inhibited the binding of [3H]DPDPE ([D-Pen(2),D-Pen(5)]enkephalin) and [3H]DAGO ([D-Ala(2),Mephe(4),Gly-ol(5)]enkephalin) to opioid receptors in mouse brain membranes. The inhibitory effect of stereoisomers of ohmefentanyl isothiocyanate at mu-opioid receptors was markedly lower than that of their parent compounds. The affinity of stereoisomers of ohmefentanyl isothiocyanate for delta-opioid receptors was, however, greater than or equal to that of their corresponding stereoisomers of ohmefentanyl. The results showed that the introduction of an isothiocyanato group into the phenyl ring in position-1 of ohmefentanyl reduced bioactivity and affinity to mu-opioid receptors but that the selectivity of these compounds for delta-opioid receptors was enhanced. Isomer (3R,4S,2'R)-ohmefentanyl isothiocyanate showed highest selectivity for delta-opioid receptors (K(i)(mu)/K(i)(delta)=13.6) and potent analgesic activity (ED(50)=0.25 mg/kg).

Analgesics, Opioid↗
PubMed2000

Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China.

BACKGROUND: Dietary isothiocyanates inhibit lung carcinogenesis in laboratory animals but human data are limited. Glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) conjugate isothiocyanates leading to more rapid elimination. Common deletion polymorphisms of GSTM1 and GSTT1 abolish enzyme activity. We hypothesised that chemopreventive effects of isothiocyanates might be heightened when enzymes that enhance their elimination are lacking. METHODS: We examined the relation between total isothiocyanate concentrations in urine, collected before diagnosis, and the subsequent risk of lung cancer among 232 incident cases of lung cancer and 710 matched controls from a cohort of 18,244 men in Shanghai, China, followed from 1986 to 1997. Homozygous deletion of the GSTM1 and GSTT1 genes were determined by PCR. FINDINGS: Individuals with detectable isothiocyanates in the urine were at decreased risk of lung cancer (smoking-adjusted relative risk for lung cancer=0.65 [95% CI 0.43-0.97]). This protective effect of isothiocyanates was seen primarily among individuals with homozygous deletion of GSTM1 (0.36 [0.20-0.63]) and particularly with deletion of both GSTM1 and GSTT1 (0.28 [0.13-0.57]). INTERPRETATION: Isothiocyanates appeared to reduce lung-cancer risk in this cohort of Chinese men. Reduction in risk was strongest among persons genetically deficient in enzymes that rapidly eliminate these chemopreventive compounds.

Case-Control Studies↗
PubMed2006

Association between consumption of cruciferous vegetables and condiments and excretion in urine of isothiocyanate mercapturic acids.

A high intake of cruciferous vegetables is associated with a reduced risk of cancer and cardiovascular diseases. This protective effect has been linked to isothiocyanates, enzymatic hydrolysis products of glucosinolates. In this study, the metabolic fate of glucosinolates and isothiocyanates after ingestion of 19 different cruciferous vegetables was studied in three male subjects. After the consumption of 13 cruciferous vegetables (glucosinolate content, 0.01-0.94 mmol/kg) and six condiments (isothiocyanate content, 0.06-49.3 mmol/kg), eight different isothiocyanate mercapturic acids were determined in urine samples. Excretion levels after the consumption of raw vegetables and condiments were higher (bioavailability, 8.2-113%) as compared to cooked vegetables (bioavailability, 1.8-43%), but the excretion rate was similar (t1/2=2.1-3.9 h). Isothiocyanates in urine remain longer at a nonzero level after the consumption of glucosinolates from cooked vegetables, as compared to raw vegetables and condiments, and maximal levels in urine were reached about 4 h later. Isothiocyanate mercapturic acids can be used as a biomarker to reflect the active dose of isothiocyanates absorbed.

Acetylcysteine↗
PubMedDate not supplied

Enzyme induction and comparative oxidative desulfuration of isothiocyanates to isocyanates.

Enzyme induction of oxidative metabolism of isothiocyanates to isocyanates by rat liver microsomes and comparative metabolic conversion of some isothiocyanates were investigated. Metabolic activity was assayed by trapping the isocyanate metabolites from isothiocyanates with the inclusion of 2-aminofluorene to form the respective mixed ureas as previously described for the 2-naphthyl isothiocyanate. Male F344 rats were fed either a conventional grain diet for induction with Aroclor 1254 or AIN 76A diet without antioxidant beginning 2 weeks before treatment with Aroclor 1254, beta-naphthoflavone, isosafrole, or phenobarbital. Enzymes responsible for the metabolism of 1- and 2-naphthyl isothiocyanate were inducible by all four agents, Aroclor being the best under the current induction protocol and metabolic conversion assay procedure. On the other hand, enzymes responsible for the metabolism of benzyl isothiocyanate were induced only by Aroclor and, to a lesser extent, by phenobarbital. For the comparative metabolic conversion studies, using the microsomes from Aroclor-treated rats fed a conventional grain diet, the rates of metabolic conversion followed the order of 1-naphthyl > > phenyl > benzyl and phenethyl > > propyl, ethyl, and methyl isothiocyanates.

Animals↗
PubMed1999

Chemoprevention of cancer by isothiocyanates, modifiers of carcinogen metabolism.

Substantial quantities of isothiocyanates are released upon consumption of normal amounts of a number of cruciferous vegetables. Some of these naturally occurring isothiocyanates such as phenethyl isothiocyanate (PEITC), benzyl isothiocyanate (BITC) and sulforaphane are effective inhibitors of cancer induction in rodents treated with carcinogens. A large amount of data demonstrate that isothiocyanates act as cancer chemopreventive agents by favorably modifying carcinogen metabolism via inhibition of Phase 1 enzymes and/or induction of Phase 2 enzymes. These effects are quite specific, depending on the structure of the isothiocyanate and carcinogen. One of the most thoroughly studied examples of isothiocyanate inhibition of rodent carcinogenesis is inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis by PEITC. This occurs because PEITC blocks the metabolic activation of NNK, resulting in increased urinary excretion of detoxified metabolites. Similar effects on NNK metabolism have been observed in smokers who consumed watercress, a source of PEITC. On the basis of these observations and knowledge of the carcinogenic constituents of cigarette smoke, a strategy for chemoprevention of lung cancer can be developed.

Animals↗
PubMed2002

[Determination of isothiocyanates and related compounds in mustard extract and horseradish extract used as natural food additives].

Amounts of isothiocyanates and related compounds in a mustard extract and a horseradish extract for food additive use were determined by GC, after confirmation of the identity of GC peaks by GC/MS. Amounts of allyl isothiocyanate, which included that of allyl thiocyanate, because most of the allyl thiocyanate detected in the sample was assumed to have been formed from allyl isothiocyanate during GC analysis, were 97.6% and 85.4%, in the mustard extract and the horseradish extract, respectively. Total amounts of the identified isothiocyanates in the mustard extract and the horseradish extract were 98.5% and 95.4%, respectively. Allyl cyanide, a degradation product of allyl isothiocyanate, was found in the mustard extract and the horseradish extract at the levels of 0.57% and 1.73%, respectively. beta-Phenylethyl cyanide, a possible degradation product of beta-phenylethyl isothiocyanate, and allyl sulfides were found in the horseradish extract, at the levels of 0.13% and 0.46%, respectively. Allylamine, which is another degradation product of allyl isothiocyanate, was determined after acetylation, and was found in the mustard extract and the horseradish extract at the levels of 8 micrograms/g and 67 micrograms/g, respectively.

Food Additives↗
PubMed1996

Phenethyl isothiocyanate, a natural chemopreventive agent, activates c-Jun N-terminal kinase 1.

Phenethyl isothiocyanate (PEITC) and other structurally related compounds are potent chemopreventive agents in a number of experimental models of cancer in animals. The mechanisms of cancer protection by these agents are not clear but may involve the regulation of gene expression, such as that by Phase II detoxifying enzymes. To unveil the upstream signaling events that lead to the potential transcriptional activation of genes, we studied the involvement of mitogen-activated protein kinase, c-Jun N-terminal kinase 1 (JNK1), and extracellular signal-regulated kinase 1 and 2 cascades, which have been shown to mediate numerous types of extracellular signals. On treatment of human ovarian HeLa cells with PEITC, JNK1 activity was strongly induced in a dose- and time-dependent manner, whereas the activation of extracellular signal-regulated kinase 1 and 2 was not substantial. Furthermore, activation of JNK1 by PEITC was inhibited by pro-oxidants hydrogen peroxide and diamide, although these two pro-oxidants by themselves had opposing effects on JNK1 activity. Pretreatment with an antioxidant, N-acetyl-L-cysteine, had no effects on PEITC activation of JNK1. When comparing the kinetics of JNK1 activation by different isothiocyanates, PEITC elicited a sustained activation, whereas 3-phenylpropyl isothiocyanate and 4-phenylbutyl isothiocyanate stimulated transient activations. The responsiveness of JNK1 to PEITC, 3-phenylpropyl isothiocyanate, and 4-phenylbutyl isothiocyanate suggests the involvement of JNK1 in the regulation of Phase II detoxifying enzyme gene expression. Furthermore, different patterns of JNK1 induction by these isothiocyanates may contribute to their distinct chemopreventive efficacies in some animal tumor model studies.

Anticarcinogenic Agents↗
PubMed1998

Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic Phase 2 enzymes.

Isothiocyanates occur in many edible plants and are consumed in substantial quantities by humans. A number of isothiocyanates block chemical carcinogenesis in a variety of animal models by inhibiting Phase 1 enzymes involved in carcinogen activation and by inducing Phase 2 enzymes that accelerate the inactivation of carcinogens. There are large but unexplained potency differences among individual isothiocyanates. When murine hepatoma (Hepa 1c1c7) and several other cell lines were exposed to low concentrations (1-5 microM) of certain isothiocyanates, the intracellular isothiocyanate/dithiocarbamate concentrations (measured by cyclocondensation with 1,2-benzenedithiol) rose rapidly (30 min at 37 degrees C) to very high levels (e.g., 800-900 microM). The intracellular accumulation of isothiocyanates/dithiocarbamates was temperature, structure, and glutathione dependent and could not be saturated under experimentally achievable conditions. When murine hepatoma cells were exposed to nine isothiocyanates (5 microM for 24 h at 37 degrees C) that differed considerably in structure and Phase 2 enzyme inducer potencies, the intracellular concentrations (area under curve) correlated closely and linearly with their potencies as inducers of the Phase 2 enzymes: NAD(P)H:quinone reductase and glutathione S-transferases. Isothiocyanates that did not accumulate to high levels were not inducers. These observations suggest strongly that induction of Phase 2 enzymes depends on intracellular levels of isothiocyanates/dithiocarbamates. Depletion of glutathione by treatment of Hepa cells with buthionine sulfoximine increased the inducer potencies of several isothiocyanates but could not be directly related to changes in intracellular isothiocyanate/dithiocarbamate concentrations, suggesting that glutathione may play several roles in the induction process.

Animals↗
PubMed1975

[Isothiocyanate and vinyl thio-oxazolidone contents of rape seeds and rape seed oil].

Comparative studies on the isothiocyanate content of rape-seeds and rape-seed oil show that, apart from nearly 300 mg/100 g of vinyl thio-oxazolidone, rape-seeds contain almost 200--300 mg/100 g of isothiocyanates of which 3-butenyl isothiocyanate and 4-pentenyl isothiocyanate (ratio of 4:1) are the main components as evidenced thin-layer and gaschromatographically. Only about 1 mg/100 g of isothiocyanates are found in pressed rape-seed oil; and but circa 10 mg/100 g, in extracted rape-seed oil. 3-Butenyl isothiocyanate and 4-pentenyl isothiocyanate (ratio of 4:1) are once more the main components. Thioglycerides are not detected in the oil. Vinyl thio-oxazolidone is found only in extracted rape-seed oil (about 2 mg/100 g).

Chromatography, Gas↗
PubMed1977

The metabolism of benzyl isothiocyanate and its cysteine conjugate.

1. The corresponding cysteine conjugate was formed when the GSH (reduced glutathione) or cysteinylglycine conjugates of benzyl isothiocyanate were incubated with rat liver or kidney homogenates. When the cysteine conjugate of benzyl isothiocyanate was similarly incubated in the presence of acetyl-CoA, the corresponding N-acetylcysteine conjugate (mercapturic acid) was formed. 2. The non-enzymic reaction of GSH with benzyl isothiocyanate was rapid and was catalysed by rat liver cytosol. 3. The mercapturic acid was excreted in the urine of rats dosed with benzyl isothiocyanate or its GSH, cysteinyl-glycine or cysteine conjugate, and was isolated as the dicyclohexylamine salt. 4. An oral dose of the cysteine conjugate of [14C]benzyl isothiocyanate was rapidly absorbed and excreted by rats and dogs. After 3 days, rats had excreted a mean of 92.4 and 5.6% of the dose in the urine and faeces respectively, and dogs had excreted a mean of 86.3 and 13.2% respectively. 5. After an oral dose of the cystein conjugate of [C]benzyl isothiocyanate, the major 14C-labelled metabolite in rat urine was the corresponding mercapturic acid (62% of the dose), whereas in dog urine it was hippuric acid (40% of the dose). 5. Mercapturic acid biosynthesis may be an important route of metabolism of certain isothiocyanates in some mammalian species.

Acetylcysteine↗
PubMed1977

Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds.

Benzyl isothiocyanate and phenethyl isothiocyanate, two compounds found in cruciferous plants, and phenyl isothiocyanate, a synthetic compound, all inhibit 7,12-dimethylbenz[a]anthracene (CMBA)-induced mammary tumor formation in female Sprague-Dawley rats when administered 4 hours prior to the DMBA. Comparable studies in which benzyl isothiocyanate was administered 24 hours before or 4 hours after DMBA showed almost complete loss of inhibition. Additions of benzyl isothiocyanate or phenethyl isothiocyanate to a diet containing CMBA inhibited formation of neoplasms of the forestomach and pulmonary adenomas in female ICR/Ha mice. Addition of benzyl isothiocyanate to a diet containing benzo[a]pyrene also inhibited carcinogenesis of the mouse forestomach due to this carcinogen. The finding of two additional anutrient dietary compounds which inhibit chemical carcinogenesis focuses on the possibility that dietary constituents of this nature may diminish the impact of exposures to chemical carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Carcinogenesis Bioassay of Allyl Isothiocyanate (CAS No. 57-06-7) in F344/N Rats and B6C3F1 Mice (Gavage Study).

A 2-year carcinogenesis bioassay of food-grade allyl isothiocyanate (greater than 93% purity), a flavoring agent, was conducted by administering 12 or 25 mg/kg allyl isothiocyanate in corn oil five times per week by gavage to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 rats and 50 mice of each sex received corn oil alone and served as vehicle controls. A single-dose study, a 14-day study, and a 13-week study were performed before the chronic study was conducted. Pathologic findings seen in the 14-day study at 50 mg/kg included a thickened mucosal surface of the stomach in rats and mice and a thickened urinary bladder wall in male mice. No gross or microscopic lesions were seen at the highest dose level (25 mg/kg) in the 13-week study. In the chronic study, survival of the dosed and control rats of each sex was comparable. Throughout the study, the mean body weights of high-dose male rats were lower than those of the controls, while during the last half of the study the mean body weights of the low-dose and high-dose female rats were higher than the mean body weights of the control animals. Final body weights in control and dosed groups were comparable. Transitional-cell papillomas in the urinary bladder occurred in dosed male rats with a statistically significant trend (P<0.05; controls, 0/49, 0%; low-dose, 2/49, 4%; high-dose, 4/49, 8%). This tumor has not been observed among 568 untreated male control F344/N rats at this laboratory. The incidence of transitional papillomas in male vehicle control rats in all laboratories in the NCI/NTP Bioassay Program is 1/994 (0.1%). Epithelial hyperplasia in the urinary bladder was also observed at increased incidences in dosed male rats (0/49, 1/49, 6/49). The hyperplasia did not occur in the same animals that had papillomas. Fibrosarcomas in the subcutaneous tissue occurred in female rats with a statistically significant positive trend (P<0.05; controls, 0/50, 0%; low-dose, 0/50, 0%; high-dose, 3/50, 6%), but the incidence in the high-dose group was not significant when compared with that in the control group. The historical incidence of this lesion is 1/591 (0.2%) in untreated control female F344/N rats at this laboratory and 9/999 (0.9%) in female gavage control rats in all laboratories in the Bioassay Program. Survival of control and dosed female mice, although comparable, was unusually low. Mean body weights of high-dose mice of each sex were higher than those of the controls throughout most of the study. Final body weights in the control and dosed groups were comparable. The mice probably did not receive the maximum tolerated dose of allyl isothiocyanate. The increased incidence of cytoplasmic vacuolization in the liver of dosed male mice was related to administration of allyl isothiocyanate (controls, 2/49, 4%; low-dose, 8/49, 16%; high-dose, 13/50, 26%). Under the conditions of this bioassay, allyl isothiocyanate was carcinogenic for male F344/N rats, causing transitional-cell papillomas in the urinary bladder. Evidence for associating allyl isothiocyanate with subcutaneous fibrosarcomas in female F344/N rats was equivocal. Allyl isothiocyanate was not carcinogenic for B6C3F1 mice of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Equivocal Male Mice: Negative Female Mice: Negative

Journal Article↗
PubMed2000

Isothiocyanates in myrosinase treated herb extract of Cleome chrysantha decne. and their antimicrobial activities.

GC/MS analysis of the volatiles produced by the action of endogenous myrosinase in Cleome chrysantha Decne. herb, showed three major components, 1-isocyano-4-methyl benzene, gamma-muurolene and (cis) nerolidole (21.72%, 12.15% and 10.39%, respectively). 1-isocyano-4-methyl benzene is not produced from myrosinase treated seeds of Cleome chrysantha Decne., while muurolene and nerolidole were found at higher concentrations 16.1% and 13.67%, respectively. Some other isothiocyanates identified in the seeds and leaves, but in low percentages, were 2-methylbutyl isothiocyanate, 4-methylthiobutyl isothiocyanate and isothiocyanatomethyl benzene. Enzymatic hydrolysis of the ethanol extract of Cleome chrysantha Decne., produced two non-volatile isothiocyanates, 4, 6-dimethyltetrahydro-1,3-oxazine-2-thione and N-(-4-methyl-sulphinyl-3-butenyl) isothiocyanate which was established by aniline and methanolic ammonia to give the stable form of phenyl thiourea. They were identified by their spectroscopic data. These two isothiocyanates and the volatiles of the herb showed good antimicrobial activity against E. coli, Pseudomonas putida and Rhizobium meloloti (gram-negative bacteria) and moderate activity against Bacillus subtilis and Streptococcus lactis (gram-positive bacteria).

Anti-Bacterial Agents↗
PubMed1995

Chemoprevention by isothiocyanates.

Naturally occurring and synthetic isothiocyanates are among the most effective chemopreventive agents known. A wide variety of isothiocyanates prevents cancer in the rat lung, mammary gland, esophagus, liver, small intestine, colon, and bladder. Mechanistic studies have shown that this chemopreventive activity is due to favorable modification of phase I and phase II carcinogen metabolism, resulting in increased carcinogen excretion or detoxification and decreased carcinogen DNA interactions. Most studies reported that the isothiocyanate must be present at carcinogen exposure in order to effect tumorigenesis inhibition. Our studies focus on naturally occurring isothiocyanates phenethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC) as lung cancer inhibitors. These studies employed the major lung carcinogens in tobacco smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BaP). Combining chemopreventive agents that inhibit tumorigenesis by NNK and BaP in rodents may be effective in addicted smokers. PEITC inhibits lung tumor induction by NNK in F-344 rats and A/J mice, while BITC inhibits BaP-induced lung tumorigenesis in A/J mice; combining the two inhibits lung tumorigenesis by combined NNK and BaP in A/J mice. PEITC selectively inhibits metabolic activation of NNK in the rodent lung, while inducing glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), one of the major NNK metabolites. Thus, PEITC decreases DNA and hemoglobin adduct formation by NNK while increasing the amounts of NNAL and its glucuronide excreted in the urine. Presently available data indicate that non-toxic doses of PEITC can inhibit the metabolic activation and carcinogenicity of NNK in rat and mouse lung; BITC has similar effects on BaP activation and tumorigenicity in mouse lung. Thus, combinations of chemopreventive agents active against different carcinogens in tobacco smoke may be useful in the chemoprevention of lung cancer.

Animals↗
PubMed1996

Quantitative determination of isothiocyanates, dithiocarbamates, carbon disulfide, and related thiocarbonyl compounds by cyclocondensation with 1,2-benzenedithiol.

A recently developed UV spectroscopic method for quantitating isothiocyanates (R-N=C=S) at the nanomole level is based on the observation that the highly electrophilic central carbon atom of the -N=C=S group can undergo successive nucleophilic additions with reagents containing two sulfhydryl groups on adjacent carbon atoms to form a cyclic thiocarbonyl product and release the nitrogen atom as a primary amine (Y. Zhang, C.-G. Cho, G. H. Posner, and P. Talalay, Anal. Biochem. 205, 100-107, 1992). The assay utilizes 1, 2-benzenedithiol as the vicinal dithiol reagent and measures the reaction product, 1,3-benzodithiole-2-thione, spectroscopically (am of 23,000 M-1 cm-1 at lambdamax = 365 nm). This paper reports a dramatic improvement in the analytical sensitivity of this method. By separating the cyclocondensation product by a simple isocratic HPLC method and using an automatic integrator, the sensitivity of detection has been lowered to a few picomoles of isothiocyanate. Furthermore, we now find that the chemical specificity of the cyclocondensation reaction is not restricted to isothiocyanates, but includes dithiocarbamates, and related thiocarbonyl compounds such as carbon disulfide, certain substituted thiourea derivatives, and xanthates. The availability of such analytical methods is important not only because isothiocyanates (and their glucosinolate precursors) are present in edible plants and are consumed by humans in substantial quantities, but also because some dithiocarbamates are toxic, and are widely used in the rubber industry as vulcanization accelerators and in agriculture as fungicides, insecticides, and herbicides. The analysis of many isothiocyanates is complicated by their extreme volatility. This difficulty can be circumvented by converting isothiocyanates quantitatively into dithiocarbamates (by facile addition of a mercaptan such as N-acetylcysteine) and quantitating the nonvolatile dithiocarbamate by the cyclocondensation reaction.

Acetylcysteine↗
PubMed1984

Antiasthmatic effects of onion extracts--detection of benzyl- and other isothiocyanates (mustard oils) as antiasthmatic compounds of plant origin.

Previous studies showed the inhibitory effects of crude ethanolic onion extracts (COE) on allergic skin reactions in man as well as on allergen-induced bronchial asthma in man and guinea-pigs. Work is in progress in order to identify both the mode of action of COE and the active substance(s). The present study describes asthma-protective effects of isothiocyanates. Groups of at least 5 guinea-pigs sensitized to ovalbumin were challenged twice (time 0 and 10 min) by the inhalation of ovalbumin 30 min after oral treatment with increasing doses of the agent tested or control solutions. Bronchial obstruction (BO) was measured by whole body plethysmography. Chloroform extracts of onions showed similar protective effects on BO as COE. The water-soluble fraction of COE was inactive. Benzyl-isothiocyanate (BITC) was identified as one component of onion lipids by combined gas chromatography/mass spectrometry. BITC inhibited BO in a dose-dependent fashion: 150 mg/kg: 89%; 75 mg/kg: 76%; 30 mg/kg: 66%; 15 mg/kg: 49%. Ethyl-isothiocyanate and allyl-isothiocyanate showed similar effects; p-hydroxy-benzyl-isothiocyanate, a very unstable mustard oil, was ineffective. Additional experiments showed no antagonistic effects of COE on histamine- or acetylcholine-induced BO. The antiasthmatic effects of onions and - perhaps - other plants may be mediated at least in part by isothiocyanates.

Administration, Oral↗
PubMedDate not supplied

Allyl isothiocyanate is mutagenic in Salmonella typhimurium.

Allyl isothiocyanate, a naturally occurring compound, component of oil of mustard and human food plants such as cabbage, cauliflower and horseradish, has up to now been regarded as nonmutagenic in bacterial mutagenicity testing systems. Recently, however, it was found to cause transitional-cell papillomas in the urinary bladder of male F344 rats. Contrary to earlier reports, in this study allyl isothiocyanate showed clear mutagenicity for Salmonella typhimurium TA100 in the preincubation assay after longer, non-standard preincubation times (greater than 20 min). The mutagenicity is expressed only in the presence of a rat-liver homogenate metabolising system, i.e. it is indirect. However, high concentrations of rat-liver homogenate suppress the mutagenicity of allyl isothiocyanate. SKF525, inhibitor of microsomal oxygenase, reduces the mutagenic potential which on the other hand is increased in the presence of 1,1,1-trichloropropene-2-oxide, inhibitor of epoxide hydrolase. This indicates the occurrence of an epoxide intermediate in allyl isothiocyanate metabolism. Another metabolic pathway, namely hydrolysis to allyl alcohol and oxidation to acrolein, a known mutagen, also seems possible as cyanamide, inhibitor of aldehyde dehydrogenase, can slightly increase the mutagenic potential. The reason(s) for allyl isothiocyanate's requirement for long preincubation times to express mutagenicity still requires elucidation, and the question arises: is allyl isothiocyanate a single, exceptional case or not?

Animals↗
PubMed2005

Analysis of glucosinolates, isothiocyanates, and amine degradation products in vegetable extracts and blood plasma by LC-MS/MS.

Dietary glucosinolates are under intensive investigation as precursors of cancer-preventive isothiocyanates. Quantitation of the dose and bioavailability of glucosinolates and isothiocyanates requires a comprehensive analysis of the major dietary glucosinolates, isothiocyanates, and related metabolites. We report a liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) analytical method for the comprehensive analysis of the seven major dietary glucosinolates, related isothiocyanates, and putative amine degradation products. The parent glucosinolates were sinigrin, gluconapin, progoitrin, glucoiberin, glucoraphanin, glucoalyssin, and gluconasturtiin. The LC-MS/MS analysis method for these compounds was developed and validated; a standard addition analysis protocol was used generally to avoid the requirement for stable isotopic standards. Where stable isotopic standards were available, internal standardization with these gave estimates in agreement with those obtained by the standard addition analysis protocol. For glucosinolates, negative ion electrospray LC-MS/MS analysis was performed. Isothiocyanates and amines were prederivatized to the corresponding thiourea and N-acetamides, respectively, and were quantified by positive ion electrospray LC-MS/MS. The limits of detection were 0.5-2 pmol; the recoveries for glucosinolates, isothiocyanates, and amines were 85-90%, 50-85%, and 60-70%, respectively; and the intra- and interbatch coefficients of variation were 1-4% and 3-10%, respectively. These methods provide facile access to comprehensive analytical data on the major dietary glucosinolates and related metabolites to quantify inputs and metabolic formation of these compounds in cancer prevention and related studies.

Amines↗