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Mustards have become an important topic of global discussion in recent years. The latest extensive reports and conference of 145 nations in Paris (January 13, 1989) reveal that several countries have stockpiled large quantities of mustard gas. This situation creates an imminent danger to accidental or intentional exposure of this gas to civil populations throughout the world. In view of the sparse literature on the toxic nature of mustard gas, we have tried to present an integrated panorama of this compound and its derivatives. In this article, efforts were made to review mustard gas--its chemical nature, mode of action, methods available for its analysis in biological fluids and target organs, absorption, distribution, metabolism and excretion and its toxicity to various organs. The effects of mustard poisoning may be local, systemic, or both, depending on environmental conditions, exposed organs, and the extent and duration of exposure. The toxic effects of mustard include inhibition of mitosis, NAD depletion, decreased tissue respiration and finally cell death. Most of the toxic effects are related to alkylation of DNA. Mustards are also selective in their accumulation in fat tissue. The immediate organs affected after mustard exposure are skin, eyes, and lungs. Sulfur mustard has also been reported to be a potent carcinogen. Burns caused by mustard are severe and require long healing periods. Depending on the type and time of exposure, mustard renders persons disabled temporarily or permanently. Various antidotes such as sodium thiosulfate, dexamethasone, promethazine, heparin, vitamin E and atropine have been recommended for combating mustard poisoning. Protective clothing can substantially reduce the toxic effects of mustard exposure. The best possible way of eliminating mustard hazard is to ban its use completely.
BACKGROUND: Although mustard is frequently consumed in Spain and elsewhere, only isolated case reports of mustard allergy have been reported. No large series of case studies have been published. OBJECTIVES: We sought to describe demographic, clinical, and immunologic characteristics of patients with mustard hypersensitivity and to determine whether any significant differences exist in age, sex, atopic family history, total immunoglobulin E (IgE) level, and specific IgE to mustard ratio among patients with differing characteristics. METHODS: Twenty-nine patients with a history of mustard allergy underwent skin prick tests with mustard, determination of total IgE, and evaluation of specific IgE to mustard. Skin prick tests with Lolium perenne, Olea europaea, and Artemisia vulgaris were done in patients with symptoms of pollinosis. The aforementioned variables were compared between various subgroups of patients for systemic versus local reactions to mustard, association versus no association with allergies to other vegetable foods, and association versus no association with pollinosis. RESULTS: The male:female ratio was 10:19. Skin prick tests to mustard were positive in all patients. The total IgE geometric mean was 189.3 kU/L. The specific IgE to mustard was positive in all patients (0.7 to > 100 kU/L). Of the 29 patients, 19 (66%) had a systemic reaction after consumption of mustard, and 10 (34%) had a local reaction; 14 (48%) had anaphylaxis. Fifteen patients (52%) had symptoms after ingestion of other vegetable foods, and 15 also had typical symptoms of pollinosis. No significant differences were found in age, sex, atopic family history, total IgE, and specific IgE to mustard between the various subgroups studied. CONCLUSIONS: Most study patients with mustard hypersensitivity had a systemic reaction and had associated pollinosis or allergy to other vegetable foods. Mustard sensitivity should be routinely tested in patients with idiopathic anaphylaxis.
BACKGROUND: Mustard allergy accounts for 1.1% of food allergies in children. However, double-blind placebo-controlled food challenge trials (DB PCFCs) have not yet been proposed. OBJECTIVE: To carry out DB PCFCs to determine the real frequency of mustard allergy in patients sensitized to mustard. METHODS: A prospective study was conducted in 30 subjects aged 3-20 years presenting positive prick tests to ground mustard seeds (Brassica nigra), mustard flour (B. juncea), metabisulfite-free strong mustard seasoning (B. juncea) and a commercialized allergenic extract (B. nigra). Twenty-seven subjects were screened for mustard-specific immunoglobulin E (IgE). PCFCs were carried out either DB or single blind (SB) with up to 1340 mg of metabisulfite-free seasoning. RESULTS: The mean diameter of the wheal induced by prick tests with the allergenic extract was lower (n.s.) than that induced by the native mustard products: 5.8 mm (1.5-15) vs 6.9 mm (0.5-18) for B. nigra ground seeds, 7.8 mm (1-20) for B. juncea flour and 9.7 mm (3-20) for the strong mustard seasoning. The diameter of the wheal induced by the allergenic extract was significantly different from that induced by the mustard seasoning (P < 0.005). The mean of mustard specific-IgE values was 8.7 KU/l (0.35-72.4). Seven of 30 food challenges were considered positive. Mean prick test results in the positive and negative PCFC subgroups were 5.5 mm vs 5.9 mm for the commercialized extract, 10.9 mm vs 5.8 mm for B. nigra ground seeds (P < 0.01), 9.9 mm vs 7.1 mm for B. juncea flour (n.s. P > 0.25) and 11.5 mm vs 9.1 mm for the metabisulfite-free mustard seasoning (n.s. P > 0.1). Mean specific IgE values determined by CAP system radioallergosorbent test (Phadebas Pharmacia) were higher but not significantly so (P > 0.25) in the subgroup with mustard allergy (12.3 K/l vs 7.6 KU/l). CONCLUSIONS: About 23.3% of the sensitized subjects were allergic to a routine dose of mustard. Positive prick tests and the presence of specific IgE were not predictive. SB PCFC or DB PCFC is required before recommending avoidance diets.
The objective of this study was to measure the uptake and metabolism of [3H]choline mustard aziridinium ion in rat brain synaptosomes. In previous investigations, we showed that this compound binds irreversibly to the choline carrier thereby inhibiting choline transport into nerve terminals; it also acts as both a substrate and inhibitor of the acetylcholine biosynthetic enzyme choline acetyltransferase. We now report that [3H]choline mustard aziridinium ion was transported into purified rat brain synaptosomes by a hemicholinium-sensitive mechanism, but at only a fraction of the rate of uptake of [3H]choline. Following 5 min incubation with the nerve terminal preparation, uptake of [3H]choline mustard aziridinium ion was 20% of that of [3H]choline transport, but this fell to 10% of [3H]choline accumulation at 30 min incubation. Apparent Michaelis constants derived from double reciprocal plots of velocity of transport versus substrate concentration revealed that the apparent affinity constants (Km) of the high-affinity choline carrier for [3H]choline mustard aziridinium ion and [3H]choline were not different (1.44 +/- 0.15 and 2.14 +/- 0.80 microM for choline and choline mustard aziridinium ion, respectively). Increasing the incubation time from 5 to 30 min, during which time a proportion of the high-affinity choline carriers were irreversibly inactivated by choline mustard aziridinium ion, did not alter the binding affinity for this compound. The maximum velocity of transport (Vmax) for the two compounds were significantly different with the maximum uptake of [3H]choline mustard aziridinium ion being 19.5% of that for choline at 5 min incubation, and falling to only 10.6% of the maximum rate of choline transport by 30 min incubation. [3H]Choline mustard aziridinium ion transported into synaptosomes on the high-affinity choline carrier was metabolized, with 27% being recovered as [3H]acetylcholine mustard aziridinium ion, 27% as [3H]phosphorylcholine mustard aziridinium ion, 7% as unmetabolized [3H]choline mustard aziridinium ion and 16% recovered as an unidentified metabolite. In parallel samples, [3H]choline taken up into synaptosomes was recovered as [3H]acetylcholine (71%) and unmetabolized [3H]choline (18%) with no net production of [3H]phosphorylcholine. Acetylation of [3H]choline mustard aziridinium ion amounted to only 7.6% of [3H]acetylcholine synthesized under the same conditions. These results show clearly that choline mustard aziridinium ion was accumulated into the cholinergic nerve terminals by the high-affinity choline carrier, but the amount was small relative to the uptake of choline and probably restricted by progressive inactivation of the transporters through covalent bond formation.
Phosphoramide mustard, an active metabolite of the anticancer drug cyclophosphamide, causes malformations in rat embryos undergoing organogenesis in vitro. The purpose of the present study was to investigate the hypothesis that apoptosis plays an important role in mediating the teratogenicity of phosphoramide mustard. Apoptosis is a process of active or programmed cell death which is characterized by internucleosomal DNA fragmentation and de novo RNA and protein synthesis. Sulphated glycoprotein-2 (SGP-2) or clusterin is induced in some models of apoptosis and is one of the proteins likely to be involved in the maintenance of cell integrity. In the present study, day 10 rat embryos were cultured for 6, 12, 24, and 45 hr, with or without the addition of 10 microM phosphoramide mustard. After culture for 24 or 45 hr with exposure to 10 microM phosphoramide mustard, the embryos were both growth-retarded and malformed. Exposure to phosphoramide mustard for 6 or 12 hr did not significantly alter the relative amounts of either the mRNA or protein for SGP-2; this treatment also had no effect on DNA fragmentation in embryos or their yolk sacs. After 24 hr in culture, the relative amounts of SGP-2 protein, but not mRNA, were increased 2-fold in the yolk sacs of the phosphoramide mustard-exposed embryos, but not in the embryos themselves. At this time, DNA fragmentation was detected in phosphoramide mustard-exposed embryos, but not in their yolk sacs or in control embryos. After 45 hr in culture, SGP-2 protein and mRNA levels were increased 2-4-fold above the controls in the phosphoramide mustard-exposed embryos and their yolk sacs. Immunohistochemical analysis revealed that in control embryos cultured for 45 hr, the SGP-2 reaction product was localized in the heart, hindgut, and yolk sac. In contrast, in phosphoramide mustard-treated embryos cultured for 45 hr, SGP-2 immunostaining was found throughout the embryo, with a strong immunoreaction in the mesenchyme and ectoplacental cone. DNA fragmentation in the embryos exposed to phosphoramide mustard for 45 hr was more extensive than that found after 24 hr, but fragmentation was still not detected in the yolk sac. Thus exposure in vitro to a teratogenic concentration of phosphoramide mustard resulted in DNA fragmentation and an increased expression of SGP-2 in the embryo. These data suggest that apoptosis is involved in mediating the teratogenicity of phosphoramide mustard.
This study was designed to investigate the individual and combined effects of mustard flour and acetic acid in the inactivation of food-borne pathogenic bacteria stored at 5 and 22 degrees C. Samples were prepared to achieve various concentrations by the addition of acetic acid (0, 0.5, or 1%) along with mustard flour (0, 10, or 20%) and 2% sodium chloride (fixed amount). Acid-adapted three-strain mixtures of Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica serovar Typhimurium strains (10(6) to 10(7) CFU/ml) were inoculated separately into prepared mustard samples stored at 5 and 22 degrees C, and samples were assayed periodically. The order of bacterial resistance, assessed by the time required for the nominated populations to be reduced to undetectable levels against prepared mustards at 5 degrees C, was S. enterica serovar Typhimurium (1 day) < E. coli O157:H7 (3 days) < L. monocytogenes (9 days). The food-borne pathogens tested were reduced much more rapidly at 22 degrees C than at 5 degrees C. There was no synergistic effect with regard to the killing of the pathogens tested with the addition of 0.5% acetic acid to the mustard flour (10 or 20%). Mustard in combination with 0.5% acetic acid had less bactericidal activity against the pathogens tested than did mustard alone. The reduction of E. coli O157:H7 and L. monocytogenes among the combined treatments on the same storage day was generally differentiated as follows: control < mustard in combination with 0.5% acetic acid < mustard alone < mustard in combination with 1% acetic acid < acetic acid alone. Our study indicates that acidic products may limit microbial growth or survival and that the addition of small amounts of acetic acid (0.5%) to mustard can retard the reduction of E. coli O157:H7 and L. monocytogenes. These antagonistic effects may be changed if mustard is used alone or in combination with >1% acetic acid.
Acetylcholine mustard aziridinium ion inhibited the transport of [3H]choline into human erythrocytes. Treatment of the erythrocytes with 1 X 10(-4) M tetraethylpyrophosphate prevented the inhibition of [3H]choline transport by acetylcholine mustard aziridinium ion. Hydrolyzed acetylcholine mustard aziridinium ion inhibited choline transport both in the presence and absence of 1 X 10(-4) M tetraethylpyrophosphate. The product of hydrolysis was equipotent with acetylcholine mustard in its ability to inhibit choline transport; incubation of this product with sodium thiosulfate prevented inhibition of choline transport thereby indicating the presence of an aziridinium ion. The hydrolysis product is likely to be choline mustard aziridinium ion. Results on the efflux of [3H]choline from erythrocytes in the presence of the proposed choline mustard aziridinium ion showed that the mustard moiety was transported into the red cells on the choline carrier. The rate of efflux of [3H]choline produced by choline mustard aziridinium ion was 55% of that produced by the same concentration of choline. It is concluded that acetylcholinesterase (EC 3.1.1.7) of red cells rapidly hydrolyzes acetylcholine mustard aziridinium ion to acetate and choline mustard aziridinium and the latter compound can act as a potent inhibitor of choline transport. This finding would indicate that the hemicholinium-like toxicity of acetylcholine mustard in the mouse is due to the formation of choline mustard aziridinium ion.
Nitrogen mustards alkylate DNA primarily at the N7 position of guanine. Using an approach analogous to that of the Maxam-Gilbert procedure for DNA sequence analysis, we have examined the relative frequencies of alkylation for a number of nitrogen mustards at different guanine-N7 sites on a DNA fragment of known sequence. Most nitrogen mustards were found to have similar patterns of alkylation, with the sites of greatest alkylation being runs of contiguous guanines, and relatively weak alkylation at isolated guanines. Uracil mustard and quinacrine mustard, however, were found to have uniquely enhanced reaction with at least some 5'-PyGCC-3' and 5'-GT-3' sequences, respectively. In addition, quinacrine mustard showed a greater reaction at runs of contiguous guanines than did other nitrogen mustards, whereas uracil mustard showed little preference for these sequences. A comparison of the sequence-dependent variations of molecular electrostatic potential at the N7-position of guanine with the sequence dependent variations of alkylation intensity for mechlorethamine and L-phenylalanine mustard showed a good correlation in some regions of the DNA, but not others. It is concluded that electrostatic interactions may contribute strongly to the reaction rates of cationic compounds such as the reactive aziridinium species of nitrogen mustards, but that other sequence selectivities can be introduced in different nitrogen mustard derivatives.
A 2-chloroethylamine derivative [N-(2-chloroethyl)-4-piperidinyl diphenylacetate (4-DAMP mustard)] of the selective muscarinic antagonist N,N-dimethyl-4-piperidinyl diphenylacetate (4-DAMP) was synthesized, and its conversion to an aziridinium ion and interaction with muscarinic receptors was investigated. When dissolved in aqueous solution at pH 7.4 and 37 degrees, 4-DAMP mustard released an equivalent amount of chloride. The release of chloride was consistent with a first-order process having a half-time of 5.7 min. The aziridinium ion reached a peak concentration at 32 min, corresponding to 75% of the initial concentration of 4-DAMP mustard. When homogenates of rat brain, heart, and submaxillary gland were incubated with 4-DAMP mustard (9 nM) for 1 hr, washed extensively, and then assayed for muscarinic receptor binding properties, a 56% decrease in the binding capacity of N-[3H]methylscopolamine in the heart and brain and a 71% decrease in the gland were observed, without a significant change in the dissociation constants. The affinity of 4-DAMP mustard and its transformation products for muscarinic receptors was determined in competitive binding experiments with N-[3H] methylscopolamine, and the results show that the aziridinium ion of 4-DAMP mustard was the most potent form, compared with the parent 2-chloroethylamine (4-DAMP mustard) and the alcoholic hydrolysis product. The rates of receptor alkylation by 4-DAMP mustard were measured in the rat heart and gland. Virtually no alkylation (less than 1%) occurred in the heart at a 4-DAMP mustard concentration of 1.6 nM, after 30 min, whereas almost 50% alkylation was observed in the gland under the same conditions. Almost complete alkylation of receptors in the gland could be achieved at a 4-DAMP mustard concentration of 200 nM, after 1 hr. Treatment of the isolated rat ileum with 4-DAMP mustard caused an irreversible blockade of contractions elicited by the muscarinic agonist oxotremorine-M, and this blockade persisted after extensive washing. The results presented here show that 4-DAMP mustard forms an aziridinium ion that binds irreversibly to muscarinic receptors and exhibits selectivity for M3, compared with M2 muscarinic receptors.
We examined the mechanism of the inflammatory response induced by topical application of mustard oil (0.5-20.0%/20 microliters per ear) to the mouse ear compared to that of the response to capsaicin. The dose-dependent increases in plasma extravasation and ear thickness reached a maximum at approximately 30 min after mustard oil application. Topical pretreatment of ears with capsaicin (250 micrograms/ear) diminished mustard oil-induced plasma extravasation for up to day 7 but not at day 14 after treatment. However, desensitization of the exudative response was not evoked by reapplication of mustard oil to ears. The inflammatory response to mustard oil did not differ between the ears of mast cell-deficient mice and those of the congenic normal mice. Mustard oil-induced plasma extravasation was unaffected by pretreatment with histamine H1 and 5-HT2 receptor antagonists and the capsaicin-functional inhibitor, ruthenium red, which inhibit capsaicin-induced ear oedema. The endopeptidase inhibitor, phosphoramidon, enhanced the ability of mustard oil to increase dye leakage. The tachykinin NK1 receptor antagonist, SR 140333 ((S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pi peridin-3-yl]ethyl]-4-phenyl-1-azoniabicyclo[2.2.2.]octane, chloride), not only inhibited mustard oil-induced plasma extravasation but also blocked the enhancement by phosphoramidon of the response to mustard oil. In contrast, the tachykinin NK2 receptor antagonist, SR 48968 ((S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4,- dichlorophenyl)butyl]benzamide), and the tachykinin NK3 receptor antagonist, SR 142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)pro pyl)-4- phenylpiperidin-4-yl)-N-methylacetamide), had no effect on plasma extravasation. The present results demonstrated that mustard oil induces mouse skin inflammation through a mechanism different from that for capsaicin. Mediators such as histamine and 5-HT from mast cells appear to be minor factors in the response to mustard oil. In addition, evidence supports the assumption that the tachykinin NK1 receptor is involved in this model.
There have been reports of chemical attacks in which sulfur mustard might have been used (a) on Iranian soldiers and civilians during the Gulf War in 1984 and 1985 and (b) in an Iraqi chemical attack on the Iranian-occupied village of Halbja in 1988, resulting in many civilian casualties. Heavy use of chemical warfare in Afghanistan by the Soviet military is a recent innovation in military tactics that has been highly successful and may ensure further use of chemical agents in future military conflicts and terrorist attacks as a profitable adjunct to conventional military arms. Mustard is a poisonous chemical agent that exerts a local action on the eyes, skin, and respiratory tissue, with subsequent systemic action on the nervous, cardiac, and digestive systems in humans and laboratory animals, causing lacrimation, malaise, anorexia, salivation, respiratory distress, vomiting, hyperexcitability, and cardiac distress. Under extreme circumstances, dependent upon the dose and length of exposure to the agent, necrosis of the skin and mucous membranes of the respiratory system, bronchitis, bronchopneumonia, intestinal lesions, hemoconcentration, leucopenia, convulsions with systemic distress, and death occur. Severe mustard poisoning in humans is associated with systemic injury, which is manifested as headache, epigastric distresses, anorexia, diarrhea, and cachexia and is usually observed at mustard doses of 1000 mg/min/m3 with damage to hematopoietic tissues and progressive leucopenia. Sulfur mustard is a cell poison that causes disruption and impairment of a variety of cellular activities that are dependent upon a very specific integral relationship. These cytotoxic effects are manifested in widespread metabolic disturbances whose variable characteristics are observed in enzymatic deficiencies, vesicant action, abnormal mitotic activity and cell division, bone marrow disruption, disturbances in hematopoietic activity, and systemic poisoning. Indeed, mustard gas readily combines with various components of the cell such as amino acids, amines, and proteins. Although evidence of an association between lung cancer and mustard gas encountered on the battlefields of World War I is at best suggestive if not problematical (Case and Lea, 1955; Beebe, 1960; Norman, 1975), the epidemiological data accumulated from the poison gas factories in Japan (Yamada et al., 1953; Wada et al., 1968; Inada et al., 1978; Shigenobu, 1980; Nishimoto et al., 1983; Hirono et al., 1984; Takuoka et al., 1986), in Germany (Weiss, 1958; Hellmann, 1970a; Weiss and Weiss, 1975; Klehr, 1984) and in England (Manning et al., 1981; Easton et al., 1988) are substantial (International Agency for Research on Cancer, 1975). Unfortunately, attempts to seek confirmatory and substantial evidence in laboratory animals such as mice (Boyland and Horning, 1949; Heston, 1950; Heston, 1953a; McNamara et al., 1975) and rats (Griffin et al., 1951; McNamara et al., 1975; Sasser et al., 1996) have not been consistent. Sulfur mustard has been shown to be mutagenic in a variety of different species using many different laboratory techniques from fruit flies, microorganisms and mammalian cell cultures (Fox and Scott, 1980). Evidence is slowly accumulating from human data (Hellmann, 1970a; Lohs, 1975; Wulf et al., 1985). Evidence for the teratogenicity of mustard has been negative in assessment of fetotoxicity and adverse effects of mustard on the reproductive potential of both human and animal studies. Indeed, investigations of women adversely affected by mustard are minimal because most of the studies have been performed on former men employees of poison gas factories and have been negative or questionable. We have recently emphasized the need to assess the affect of a suspected teratogen on maternal toxicity in laboratory animals before any conclusions can be made.(ABSTRACT TRUNCATED)
Nitrogen mustard and its derivatives such as cyclophosphamide, chlorambucil and melphalan are widely used anti-cancer agents, despite their non-specific reaction mechanism. In this study, the effect of alkylation by nitrogen mustard of DNA and RNA (coding for a single protein) was investigated using both a translation system and a coupled transcription/translation system. When alkylated DNA was used as the template for coupled transcription and translation, a single translation product corresponding to the 62 kDa luciferase protein was synthesised. Production of the translated product encoded by this template was inhibited by mustard concentrations as low as 10 nM, and 50% inhibition occurred with 30 nM mustard. A primer extension assay employed to verify alkylation sites on the DNA revealed that all guanine residues on the DNA template are susceptible to alkylation by nitrogen mustard. Similarly, when alkylated RNA was used as the template for protein synthesis, the amount of the 62 kDa luciferase protein decreased with increasing mustard concentration and a range of truncated polypeptides was synthesised. Under these conditions 50% inhibition of translation occurred with approximately 300 nM mustard (i.e. approximately 10 times that required for similar inhibition using an alkylated DNA template). Furthermore, a gel mobility shift assay revealed that mustard alkylation of the RNA template results in the formation of a more stable retarded RNA complex. The functional activity of the luciferase protein decreased with alkylation of both the DNA and RNA templates, with a half-life of loss of activity of 1.1 h for DNA exposed to 50 nM mustard, and 0.5 h for RNA exposed to 50 microM mustard. The data presented support the notion that DNA is a critical molecule in the mode of action of mustards.
As there is a strong correlation between diet and cancer, the dietary constituents that inhibit mutagenesis and/or carcinogenesis are of paramount importance for the prevention of human cancer. In the present study, cancer chemopreventive potentials of different doses of mustard (Brassica compestris) seed mixed diets were evaluated against benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis and 3-methylcholantrene (MCA)-induced uterine cervix tumorigenesis. Results showed a significant inhibition of stomach tumour burden (tumours/ mouse) by mustard seeds. Tumour burden was 7.08 +/- 2.47 in the B(a)P-treated control group, whereas it was reduced to 1.36 +/- 1.12 (P<0.001) by the 2.5% dose and 1.18 +/- 0.87 (P<0.001) by the 5% dose of mustard seeds. The cervical carcinoma incidence, as compared to MCA-treated control group (73.33%), was reduced to nil (P<0.05) by the 5% diet of mustard seeds and to 13.33% (P<0.05) by the 7.5% diet of mustard seeds. The effect of the 2.5% and 5% mustard seed mixed diets was also examined on the antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH) and lipid peroxidation in the liver of Swiss albino mice. The glutathione-S-transferase-specific activity was increased (P<0.05) by the 2.5% dose, whereas there was no significant change in the activity of DT-diaphorase. In antioxidant systems, significant elevation of the specific activities of superoxide dismutase and catalase was observed with both doses of mustard seeds (P<0.05). The level of reduced glutathione (GSH) measured as nonprotein sulphydryl content was elevated by the 2.5% dose of mustard seeds only (P<0.05). Lipid peroxidation measured as formation of thiobarbituric acid reactive substances production showed significant inhibition (P<0.05) by the 5% dose of mustard seed mixed diet. LDH activity was decreased significantly (P<0.05) by both the doses. The results strongly suggest the cancer chemopreventive potentials of mustard seeds and their ability to enhance the antioxidant defence system and in turn provide protection against the toxic effects of carcinogens. It is likely that the use of mustard seeds in the diet may contribute to reducing the risk of cancer incidence and burden in the human population.
This study was undertaken to determine whether the glucosinolates naturally present in non-deheated mustard flour could serve as a source of allyl and other isothiocyanates in sufficient quantity to kill Escherichia coli O157:H7 inoculated in ground beef at three different levels, during refrigerated storage of the meat under nitrogen. Mustard flour was mixed at 5%, 10% or 20% (w/w) with freshly ground beef, then the beef was inoculated with a cocktail of five strains of E. coli O157:H7 at either 3, 6 or < or =1.6 log10 cfu/g. The ground beef was formed into 100 g patties and each was placed in a bag of Nylon/EVOH/PE, which was back-flushed with 100% N2, heat-sealed and stored at 4 degrees C for < or =21 days. During storage, the allyl isothiocyanate (AIT) levels in package headspaces were determined by gas liquid chromatography. By 21 days, the levels present in treatments were not significantly different. After 21 days storage, there were 0.5, 3 and 5.4 log10 decreases in numbers of E. coli O157:H7 from the initial levels of 6 log10 cfu/g in meat containing 5%, 10% and 20% mustard flour, respectively. When inoculated at 3 log10 cfu/g, E. coli O157:H7 was reduced to undetectable levels after 18, 12 and 3 days with 5%, 10% and 20% mustard flour, respectively. When immunomagnetic separation (IMS) was used for E. coli recovery following its inoculation at < or =1.6 log10 cfu/g, 5% mustard did not completely eliminate the pathogen from ground beef stored for 6 days. The natural microflora of the ground beef which developed in vacuum packages was unaffected by the addition of 5% mustard flour but some inhibition was found at higher concentrations. Sensory evaluation of the cooked ground beef showed that there were no significant differences in the acceptability of meat treated with 5 or 10% mustard flour. However, panelists could distinguish untreated controls from mustard treatments, but considered the mustard-treated meat to be acceptable. These results showed that it is possible to use mustard flour at levels of >5-10% to eliminate E. coli O157:H7 from fresh ground beef.
Topical application of mustard oil (allyl isothiocyanate) to the skin or injection into joints induces hyperalgesia, allodynia, and neuroinflammation. However, when applied to the oral or nasal mucosa, mustard oil evokes a desensitizing pattern of irritation. Presently we investigated the responses of neurons in superficial laminae of trigeminal subnucleus caudalis (Vc) to noxious thermal (53 degrees C) and chemical (pentanoic acid; 200 mM) stimuli prior to and following lingual mustard oil application. A low concentration of mustard oil (0.125%) applied by constant flow (0.5 ml/min; 15 min), initially excited Vc neurons followed by partial desensitization. Responses to noxious heat were unchanged following mustard oil. A high concentration of mustard oil (1.25%) initially excited Vc neurons followed quickly (within 20 s) by nearly complete desensitization. The desensitization was transient since reapplication of mustard oil approximately 20 min later elicited a comparable response that also rapidly desensitized. Mustard oil also transiently cross-desensitized Vc responses to pentanoic acid (to 52%), in striking contrast to noxious heat-evoked responses which were significantly sensitized to approximately 160% of pre-mustard oil levels. The data suggest that the effect of mustard oil on subsequent lingual nociceptive responses is concentration dependent, transient, and modality specific.
We investigated the temporal pattern of oral irritation elicited by sequential application of mustard oil (allyl-isothiocyanate), and whether it exhibits self-desensitization and cross-desensitization with capsaicin. Mustard oil (0.125%, 40 micro l) was sequentially applied to one side of the tongue at 1 min intervals, and subjects rated the intensity of the irritant sensation elicited by each stimulus. Ratings successively declined across trials, indicating desensitization. In contrast, sequential application of capsaicin (10 ppm) elicited irritation that increased in intensity across trials (sensitization). To test for self-desensitization by mustard oil, a 10 min hiatus was imposed following the series of unilateral mustard oil stimuli, after which mustard oil was applied to both sides of the tongue. In a two-alternative forced-choice paradigm, subjects chose which side had stronger irritation and also independently rated the irritant intensity on each side. A significant majority of subjects chose the side not previously receiving mustard oil as more intense, and assigned significantly higher intensity ratings to that side, indicating self-desensitization. In two additional sessions, the same paradigm was used to show mustard oil cross-desensitization of irritation elicited by capsaicin, and capsaicin cross-desensitization of irritation from mustard oil. In a final session, sequential application of mustard oil at faster (20 s) intervals initially evoked a sensitizing pattern followed by desensitization. The temporal patterns of oral irritation exhibited by mustard oil, and its reciprocal cross-desensitization with capsaicin, are similar to those of menthol and nicotine.