Could Nitrile Derivatives of Turnip (Brassica rapa) Glucosinolates Be

Perspective pubs.acs.org/JAFC

Could Nitrile Derivatives of Turnip (Brassica rapa) Glucosinolates Be Hepato- or Cholangiotoxic in Cattle? Mark G. Collett,*,† Bryan L. Stegelmeier,‡ and Brian A. Tapper§ †

Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North 4442, New Zealand Poisonous Plant Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Logan, Utah 84341, United States § AgResearch Ltd., Palmerston North 4442, New Zealand ‡

ABSTRACT: Turnip (Brassica rapa ssp. rapa) and rape (Brassica napus ssp. biennis) and other brassica forage crops are regarded as “safe” feed for cattle during late summer and fall in the North Island of New Zealand when high Pithomyces chartarum spore counts in pastures frequently lead to sporidesmin toxicity (facial eczema). Sporadic acute severe cases of turnip photosensitization in dairy cows characteristically exhibit high γ-glutamyl transferase and glutamate dehydrogenase serum enzyme activities that mimic those seen in facial eczema. The two diseases can, however, be distinguished by histopathology of the liver, where lesions, in particular those affecting small bile ducts, differ. To date, the hepato-/cholangiotoxic phytochemical causing liver damage in turnip photosensitization in cattle is unknown. Of the hydrolysis products of the various glucosinolate secondary compounds found in high concentrations in turnip and rape, work has shown that nitriles and epithionitriles can be hepatotoxic (and nephro- or pancreatotoxic) in rats. These derivatives include β-hydroxy-thiiranepropanenitrile and 3-hydroxy-4pentenenitrile from progoitrin; thiiranepropanenitrile and 4-pentenenitrile from gluconapin; thiiranebutanenitrile and 5hexenenitrile from glucobrassicanapin; phenyl-3-propanenitrile from gluconasturtiin; and indole-3-acetonitrile from glucobrassicin. This perspective explores the possibility of the preferential formation of such derivatives, especially the epithionitriles, in acidic conditions in the bovine rumen, followed by absorption, hepatotoxicity, and secondary photosensitization. KEYWORDS: turnip, Brassica rapa, glucosinolate, nitrile, epithionitrile, hepatotoxin, bile duct, bovine

■

hyperplasia, eccentric subintimal fibroblastic proliferation of portal blood vessels, and eventually bridging portal fibrosis. In turnip photosensitization there is microscopic cholangiectasis with attenuation of biliary epithelium in some ducts (Figure 1A), irregular regeneration of biliary epithelium in others, obliteration of other small ducts by unrecognizable debris or scar tissue, peribiliary concentric fibrosis (Figure 1B), and a paucity of excessive portal tract fibrosis or bile duct hyperplasia.3 At present, the hepato- and cholangiotoxic phytochemical derivatives causing such liver damage are unknown. Brassica spp. contain a large variety of secondary compounds, and the principal ones are the sulfur-containing glucosinolates (GSLs). The purpose of this perspective is to address the present state of knowledge regarding the GSL secondary compounds in turnips and forage rape, and their derivatives, in particular, the nitriles and epithionitriles, and the possible role of the latter in the causation of liver injury in cattle.

INTRODUCTION In New Zealand, as in other countries, turnip (Brassica rapa ssp. rapa orrapifera), rape (Brassica napus ssp. biennis), and other fast-growing brassica forage crops are often utilized to provide high-quality, readily digestible cattle feed. On the North Island such crops are generally regarded as “safe” for cattle during late summer and autumn (fall) when alternative perennial ryegrass (Lolium perenne)-dominated pastures frequently develop high Pithomyces chartarum spore counts that are associated with sporidesmin toxicity (facial eczema). However, occasionally these brassica forages may be toxic as they have been associated with a number of diseases including photosensitization.1,2 Toxicity on brassica is not associated with sporidesmin as no spores have yet been found on brassica leaf litter.2 Similarities in presentation and clinical disease present difficulties when an effort is made to distinguish turnip photosensitization from facial eczema. Serum samples from dairy cows with severe brassica-associated photosensitization generally reveal markedly elevated γ-glutamyl transferase (GGT) and glutamate dehydrogenase (GDH) serum enzyme activities similar to those seen in facial eczema. In both diseases, the type of photosensitization is secondary to liver damage, with phytoporphyrin (phylloerythrin) being the photodynamic agent.2 However, the histopathological changes seen in the liver of subacute cases of the respective diseases are unique and diagnostic.3 In facial eczema, lesions in the liver are characterized by varying degrees of necrosis of medium-sized and larger bile ducts, concentric peribiliary fibrosis, bile duct © 2014 American Chemical Society

Special Issue: Poisonous Plant Symposium, Inner Mongolia Received: Revised: Accepted: Published: 7370

January 29, 2014 March 28, 2014 March 29, 2014 March 29, 2014 dx.doi.org/10.1021/jf500526u | J. Agric. Food Chem. 2014, 62, 7370−7375

Journal of Agricultural and Food Chemistry

Perspective

Figure 1. (A) Photomicrograph of the liver of a cow that had grazed a turnip crop and that had been photosensitive for 9 days. The dilated small bile duct (left of center) is lined by an abnormally thin, attenuated epithelium and surrounded by a thin band of concentric fibrosis. A normal portal vein (right of center) and a small arteriole between the vein and bile duct are also visible. (B) Photomicrograph of the liver of another cow that had grazed a turnip crop and that had been photosensitive for 16 days. Two small bile ducts are present in the center, and both are surrounded by a moderately thick band of concentric fibrosis. A normal arteriole is visible top right. H&E 40×.

■

GLUCOSINOLATES (GSLS) AND THEIR DEGRADATION PRODUCTS GSLs (mustard oil glucosides) are biosynthesized from certain amino acids and are composed of a β-D-thioglucose group linked to a sulfonated aldoxime. Nearly 130 unique glucosinolates with elongated and modified amino acid-derived side chains4 have been described. GSLs are classified as aliphatic, aromatic, or indolic depending on whether the derived amino acids are aliphatic (methionine, alanine, valine, leucine, isoleucine), aromatic (tyrosine, phenylalanine), or indolic (tryptophan).5 There are a large number of GSLs in turnip and rape varieties grown around the world, but the six that occur in the highest concentrations are (i) progoitrin (2hydroxy-3-butenyl GSL), (ii) gluconapin (3-butenyl GSL), and (iii) glucobrassicanapin (4-pentenyl GSL), all three of which are in the alkenyl (terminally unsaturated carbon in the sidechain) subgroup of the aliphatic GSL, plus (iv) gluconasturtiin (2-phenylethyl), an aromatic GSL, as well as the indolic GSLs (v) glucobrassicin and (iv) neoglucobrassicin.6−11 In New Zealand, progoitrin would appear to be the dominant GSL,12 whereas gluconapin, glucobrassicanapin, and gluconasturtiin tend to be more dominant elsewhere.8,10 Another aliphatic GSL worth mentioning is sinigrin (2-propenyl GSL), which is found in high concentrations in Brassica oleracea (kale, cabbage, cauliflower, broccoli, Brussels sprouts) and Brassica nigra (black mustard), and in small amounts in turnips and rape.9 Intact GSLs are stable, nontoxic compounds found in all plant tissues in Brassica spp. When plant cells are crushed during cutting or chewing, the GSLs come in contact with the myrosinase enzyme system, leading to rapid generation of unstable thiohydroximate-O-sulfonate intermediates and spontaneous Lossen rearrangement of the core structure to form the isothiocyanate and, in the case of progoitrin GSL, the oxazolidine-2-thione (goitrin). This process is sometimes called the “mustard oil bomb”.4 In vitro experiments have shown that the interaction of nitrile-specifier protein, epithiospecifier protein, and epithiospecifier-modifier protein act as nonenzymic cofactors that, in the presence of ferrous ions, drive the hydrolysis of specific GSLs toward the production of nitriles (organic cyanides) and epithionitriles.13−16 As far as is known, however, no in vivo work has yet been done to establish whether these proteins are functional in the rumen. Low pH (4−6) also favors nitrile formation.17,18 Conceivably, it is also possible that microbiota with myrosinase activity, such as lactic

acid bacteria, could further contribute to heightened nitrile/ epithionitrile production in the rumen.19 Other hydrolysis derivatives include thiocyanates, glucose, elemental sulfur, and ascorbigens.18,20−22 Isothiocyanates are regarded as the most active GSL derivatives but are often volatile, highly reactive, and unstable; nitriles, on the other hand, are less reactive but more stable.23 A diagrammatic representation of this process is shown in Figure 2. The majority of the degradation products that result from the presence of intact GSLs in the rumen under weakly acid pH conditions are nitriles.24 Furthermore, nitriles can be produced from GSLs by the action of Fe2+ under similar pH conditions.23 Epithionitriles, characterized by the cyclic thiirane (episulfide)

Figure 2. Generic diagram of glucosinolate (GSL) hydrolysis following tissue damage and myrosinase enzyme activity (“the mustard oil bomb”) with the respective derivatives (based on Wittstock and Halkier).5 At neutral pH the unstable thiohydroximate-O-sulfonate rearranges to form the isothiocyanate or the oxazolidine-2-thione (goitrin) if the R-group is hydroxylated at carbon 3. In some GSL, a thiocyanate-forming protein (TFP) drives the formation of thiocyanate. Nitriles and epithionitriles tend to be derived when certain cofactors, such as nitrile-specifier protein (NSP), epithiospecifier protein (ESP), and ferrous ions, plus low pH, are present. 7371

dx.doi.org/10.1021/jf500526u | J. Agric. Food Chem. 2014, 62, 7370−7375


Perspective

Table 1. Parent Glucosinolates, Together with Their Nitrile and Epithionitrile Derivativesa

a The first name for each compound is the systematic name26 and the one used in the text. One or more synonyms, sometimes used in references, for each compound, together with the chemical formula and structure are also shown.

■

moiety, can be derived only from the alkenyl subgroup of the aliphatic GSLs.16,25 The following nitriles and epithionitriles, using systematic nomenclature,26 are potentially derived: (R)-3hydroxy-4-pentenenitrile plus two diastereomeric (2R)-βhydroxy-thiiranepropanenitriles from progoitrin; 4-pentenenitrile and thiiranepropanenitrile from gluconapin; and 5hexenenitrile and thiiranebutanenitrile from glucobrassicanapin.21,27−30 Additional nitrile derivatives potentially derived from turnips and rape include phenyl-3-propanenitrile from gluconasturtiin and indole-3-acetonitrile from glucobrassicin.31−33 Of these nitriles, the most stable is 3-hydroxy-4pentenenitrile from progoitrin.21 The class, trivial name, synonym(s), and formula of the GSLs in turnips and rape, as well as the systematic names, synonyms, formulas, and structures of their respective nitrile and epithionitrile derivatives are shown in Table 1.

NITRILE AND EPITHIONITRILE TOXICITY STUDIES IN RATS AND MICE

In mice, the nitrile derivatives of progoitrin GSL are about 8 times as toxic as the oxazolidinethione derivative, goitrin.34 Rats fed diets containing mixed nitriles developed liver lesions (bile duct hyperplasia, fibrosis, megalocytosis, and zonal necrosis) and kidney lesions (megalocytosis of renal tubular epithelial cells).35 Similar dose-dependent lesions, associated with serum biochemical alterations indicative of hepatocellular damage and cholestasis, were induced in rats that were fed diets containing the diastereoisomers of (2S)-β-hydroxy-thiiranepropanenitrile for 3 months.36 The authors in this study described hepatic changes similar to those seen after ingestion of aflatoxin or pyrrolizidine alkaloids, as well as biliary hyperplastia with “flattened epithelium and dilated lumina”36 of affected bile ducts. The latter changes are reminiscent of the microscopic cholangiectasis seen in a turnip-poisoned cow (Figure 1A). 7372



■

Perspective

NITRILE AND EPITHIONITRILE STUDIES IN RUMINANTS 3-Butenenitrile, a derivative of the glucosinolate sinigrin, has been shown to cause minor liver damage as indicated by slightly raised GGT activities when given orally to sheep. The liver lesions were not characterized histologically.55,56 The analysis of samples of fat, liver, kidney, and muscle from slaughtered beef cattle that had been fed a ration containing up to 10% crambe (Crambe abyssinica) seed meal, which would be expected to contain high levels of crambene (3-hydroxy-4pentenenitrile),57 failed to detect any GSL derivatives.58 In ruminants grazing brassica crops, the dose of derived nitriles and epithionitriles will depend both on the amount produced via enzymatic hydrolysis during chewing and rumination and on the amount produced nonenzymatically in the presence of low rumen pH and ferrous ions. Certainly, additional metabolism including microbial degradation in the rumen and the nature, concentration, and reactivity of, and host tolerance to, the respective compounds will influence disease development.23,24 Further work on the mechanism by which nitriles and epithionitriles exert potentially noxious effects on hepatocytes and biliary epithelium is needed. An aspect that will also need investigation in future cases is whether a lowered rumen pH, associated with subacute ruminal acidosis induced by the low neutral detergent fiber and high water-soluble carbohydrate content of forage brassica, contributes to greater nitrile or epithionitrile elaboration in the rumen.12,59 In conclusion, distinctive bile duct lesions can occur in cattle that develop photosensitization following grazing on turnip or rape forage crops. To date, the identity of the hepato- or cholangiotoxic phytochemical(s) in such toxic forage brassica remains undiscovered. Various nitrile and epithionitrile derivatives of GSL found in crop plants have been shown to be hepatic, renal, pancreatic, and/or gastric toxins in rats. Because of this, it is hypothesized that one or more of these GSL derivatives, in particular those with the thiirane episulfide moiety (the epithionitriles), could be toxic to the livers of cattle under certain circumstances, such as when rumen pH is acidic. Research on the potential toxicity of these compounds, either through the dosing of pure compounds or through the creation of rumen conditions conducive to their formation in high concentrations (low pH, ferrous ions) from ingested brassica forage, is warranted.

The derivatives responsible for the nephrotoxicity in rats were identified as (2S)-β-hydroxy-thiiranepropanenitrile and thiiranepropanenitrile.37−39 It is not clear whether the renal lesions are due to released cyanide, terminal hypoxia, the epithio group, the nitrile itself, or oxidation products of the aliphatic moiety.38−40 In another experiment, administration of thiiranepropanenitrile to rats caused severe toxicity, characterized by periacinar hepatic necrosis and renal tubular degeneration.40 Degeneration and necrosis of the forestomach epithelium of rats dosed with thiiranepropanenitrile have also been described.39 Another less potent nitrile derived from progoitrin, 3hydroxy-4-pentenenitrile, is a selective pancreatotoxin, causing apoptosis and necrosis in individual exocrine acinar cells in rats treated for 4 days.41 This may be related to the duration and route of exposure as subcutaneous injections of this nitrile into pregnant rats induced liver necrosis and bile duct hyperplasia after 12 days.37 In contrast, the closely related 4-pentenenitrile derivative from gluconapin GSL appears to be nontoxic in rats.40 A large number of aliphatic nitrile compounds are utilized in industrial applications and manufacturing, and some of these products produce central nervous system, hepatic, cardiovascular, renal, or gastrointestinal toxicity. Acrylonitrile, for example, is a known mutagen, animal carcinogen, and suspected human carcinogen. It and the structurally similar methacrylonitrile are eliminated unchanged in expired air, as well as via a variety of urinary metabolites. The principal metabolites in bile are glutathione conjugates, whereas oxidation by cytochrome P450 enzymes to an epoxide intermediate could lead to the release of cyanide.42 With regard to nitrile compounds that could potentially be hepato- or cholangiotoxic in cattle, attention is drawn to the epithionitrile derivatives. The latter are thiirane molecules (1,2episulfides) that are rarely encountered in nature.43 Chemically, they are similar to epoxides and would be expected to bind covalently to proteins and to DNA and thus could act as alkylating agents with cytotoxic, mutagenic, and carcinogenic effects.40,44−46 In addition, they could react with a wide variety of electrophilic and nucleophilic compounds, as well as undergo polymerization.40,47 Polymerized thiiranepropanenitrile appeared to be relatively nontoxic when administered in high doses to rats.40 In the rat, thiiranepropanenitrile is rapidly absorbed irrespective of route of administration. It is bioactivated following conjugation to glutathione and excreted predominantly as a mercapturic acid in urine with smaller amounts in bile.46,48,49 It has been suggested that the threemembered thiirane ring is partially responsible for the toxicity of the epithionitriles.50 In addition, it is possible that the slow liberation of hydrogen cyanide may make some contribution to the toxicity of epithionitriles.46 In humans, there are reports of convulsions and fatalities following respiratory arrest ascribed to a variety of aliphatic nitriles that are structurally similar to 3-hydroxy-4pentenenitrile.51 Experiments with mice inoculated intraperitoneally show that these nitriles release free cyanide after hepatic microsomal biotransformation of the cyano group.51 It has been suggested that cyanide levels in the brain play an important role in mortality.52 For aliphatic nitriles, the length of the carbon chain, the position of a double bond, and the presence of an α-hydrogen atom are determinants of the extent of metabolism of nitriles to CN−.53,54

■

AUTHOR INFORMATION

Corresponding Author

*(M.G.C.) Phone: +64 6 356 9099. Fax: +64 6 350 5714. Email: [email protected]. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS Stimulating discussions on the possible roles of epithionitriles in the induction of bile duct and/or hepatocyte lesions in cows were held with Rex Munday, AgResearch Hamilton, New Zealand. We thank Colleen Blair, Hayley Dann, and John Munday for assistance.

■

ABBREVIATIONS USED GGT, γ-glutamyl transferase; GDH, glutamate dehydrogenase; GSL, glucosinolate 7373



■

Perspective

(22) Cartea, M. E.; Velasco, P. Glucosiniolates in Brassica foods: bioavailability in food and significance for human health. Phytochem. Rev. 2008, 7, 213−229. (23) Bellostas, N.; Sørensen, A. D.; Sørensen, J. C.; Sørensen, H. Fe2+ catalyzed formation of nitriles and thionamides from intact glucosinolates. J. Nat. Prod. 2008, 71, 76−80. (24) Forss, D. A.; Barry, T. N. Observations on nitrile production during autolysis of kale and swedes, and their stability during incubation with rumen fluid. J. Sci. Food Agric. 1983, 34, 1077−1084. (25) Bones, A. M.; Rossiter, J. T. The myrosinase-glucosinolate system, its organization and biochemistry. Physiol. Plant. 1996, 97, 194−208. (26) U.S. National Library of Medicine, ChemIDplus, http://www. chem.sis.nlm.nih.gov/chemidplus (accessed Jan 30, 2014). (27) Daxenbichler, M. E.; VanEtten, C. H.; Tallent, W. H.; Wolff, I. A. Rapeseed meal autolysis. Formation of diastereomeric (2R)-1cyano-2-hydroxy-3,4-epithiobutanes from progoitrin. Can. J. Chem. 1967, 45, 1971−1974. (28) Daxenbichler, M. E.; VanEtten, C. H.; Wolff, I. A. Diastereomeric episulfides from epi-progoitrin upon autolysis of crambe seed meal. Phytochemistry 1968, 7, 989−996. (29) VanEtten, C. H.; Daxenbichler, M. E. Formation of organic nitriles from progoitrins in leaves of Crambe abyssinica and Brassica napus. J. Agric. Food Chem. 1971, 19, 194−195. (30) Kirk, J. T. O.; MacDonald, C. G. 1-Cyano-3,4-epithiobutane: a major product of glucosinolate hydrolysis in seeds from certain varieties of Brassica campestris. Phytochemistry 1974, 13, 2611−2615. (31) Cole, R. A. Isothiocyanates, nitriles and thiocyanates as products of autolysis of glucosinolates in Cruciferae. Phytochemistry 1976, 15, 759−762. (32) Daxenbichler, M. E.; VanEtten, C. H.; Spencer, G. F. Glucosinolates and derived products in cruciferous vegetables. Identification of organic nitriles from cabbage. J. Agric. Food Chem. 1977, 25, 121−124. (33) McDanell, R.; McLean, A. E. M.; Hanley, A. B.; Heaney, R. K.; Fenwick, G. R. Chemical and biological properties of indole glucosinolates (glucobrassicins): a review. Food Chem. Toxicol. 1988, 26, 59−70. (34) VanEtten, C. H.; Daxenbichler, M. E.; Wolff, I. A. Natural glucosinolates (thioglucosides) in foods and feeds. J. Agric. Food Chem. 1969, 17, 483−491. (35) VanEtten, C. H.; Gagne, W. E.; Robbins, D. J.; Booth, A. N.; Daxenbichler, M. E.; Wolff, I. A. Biological evaluation of crambe seed meals and derived products by rat feeding. Cereal Chem. 1969, 46, 145−155. (36) Gould, D. H.; Gumbmann, M. R.; Daxenbichler, M. E. Pathological changes in rats fed the crambe meal-glucosinolate hydrolytic products, 2S-1-cyano-2-hydroxy-3,4-epithiobutanes (erythro and threo) for 90 days. Food Cosmet. Toxicol. 1980, 18, 619−625. (37) Nishie, K.; Daxenbichler, M. E. Toxicology of glucosinolates, related compounds (nitriles, R-goitrin, isothiocyanates) and vitamin U found in Cruciferae. Food Cosmet. Toxicol. 1980, 18, 159−172. (38) Gould, D. H.; Fettman, M. J.; Daxenbichler, M. E.; Bartuska, B. M. Functional and structural alterations of the rat kidney induced by the naturally occurring organonitrile 2S-1-cyano-2-hydroxy-3,4-epithiobutane. Toxicol. Appl. Pharmacol. 1985, 78, 190−201. (39) Wallig, M. A.; Gould, D. H.; Fettman, M. J.; Willhite, C. C. Comparative toxicities of the naturally occurring nitrile 1-cyano-3,4epithiobutane and the synthetic nitrile n-valeronitrile in rats: differences in target organs, metabolism and toxic mechanisms. Food Chem. Toxicol. 1988, 26, 149−157. (40) Dietz, H. M.; Panigrahi, S.; Harris, R. V. Toxicity of hydrolysis products from 3-butenyl glucosinolate in rats. J. Agric. Food Chem. 1991, 39, 311−315. (41) Wallig, M. A.; Gould, D. H.; Fettman, M. J. Selective pancreatotoxicity in the rat induced by the naturally occurring plant nitrile 1-cyano-2-hydroxy-3-butene. Food Chem. Toxicol. 1988, 26, 137−147.

REFERENCES

(1) Morton, J. M.; Campbell, P. H. Disease signs reported in southeastern Australian dairy cattle while grazing Brassica species. Aust. Vet. J. 1997, 75, 109−113. (2) Collett, M. G.; Matthews, Z. M. Photosensitivity in cattle grazing Brassica crops. Int. J. Poisonous Plant Res. 2013, 3, xx−yy (in press). (3) Collett, M. G. Bile duct lesions associated with turnip (Brassica rapa) photosensitization compared to those due to sporidesmin toxicosis in dairy cows. Vet. Pathol. 2014, DOI: 10.1177/ 0300985813513042. (4) Grubb, C. D.; Abel, S. Glucosinolate metabolism and its control. Trends Plant Sci. 2006, 11, 89−100. (5) Wittstock, U.; Halkier, B. A. Glucosinolate research in the Arabidopsis era. Trends Plant Sci. 2002, 7, 263−270. (6) Carlson, D. G.; Daxenbichler, M. E.; VanEtten, C. H.; Tookey, H. L.; Williams, P. H. Glucosinolates in crucifer vegetables: turnips and rutabagas. J. Agric. Food Chem. 1981, 29, 1235−1239. (7) Carlson, D. G.; Daxenbichler, M. E.; Tookey, H. L.; Kwolek, W. F.; Hill, C. B.; Williams, P. H. Glucosinolates in turnip tops and roots: cultivars grown for greens and/or roots. J. Am. Soc. Hortic. Sci. 1987, 112, 179−183. (8) Matthäus, B.; Luftmann, H. Glucosinolates in members of the family Brassicaceae: separation and identification by LC/ESI-MS-MS. J. Agric. Food Chem. 2000, 48, 2234−2239. (9) Kim, S.-J.; Ishida, M.; Matsuo, T.; Watanabe, M.; Watanabe, Y. Separation and identification of glucosinolates of vegetable turnip rape by LC/APCI-MS and comparison of their contents in ten cultivars of vegetable turnip rape (Brassica rapa L.). Soil Sci. Plant Nutr. 2001, 47, 167−177. (10) Zukalová, H.; Vašaḱ , J.; Nerad, D.; Štranc, P. The role of glucosinolates of Brassica genus in the crop system. Rostlinna Vyroba 2002, 48, 181−189. (11) Padilla, G.; Cartea, M. E.; Velasco, P.; De Haro, A.; Ordás, A. Variation of glucosinolates in vegetable crops of Brassica rapa. Phytochemistry 2007, 68, 536−545. (12) Barry, T. N. The feeding value of forage brassica plants for grazing ruminant livestock. Anim. Feed Sci. Technol. 2013, 181, 15−25. (13) Tookey, H. L. Crambe thioglucoside glucohydrolase (EC 3.2.3.1): separation of a protein required for epithiobutane formation. Can. J. Biochem. 1973, 51, 1654−1660. (14) MacLeod, A. J.; Rossiter, J. T. The occurrence and activity of epithiospecifier protein in some Cruciferae seeds. Phytochemistry 1985, 24, 1895−1898. (15) Bernardi, R.; Negri, A.; Ronchi, S.; Palmieri, S. Isolation of the epithiospecifier protein from oil-rape (Brassica napus ssp. oleifera) seed and its characterization. FEBS Lett. 2000, 467, 296−298. (16) Kissen, R.; Bones, A. M. Nitrile-specifier proteins involved in glucosinolate hydrolysis in Arabidopsis thaliana. J. Biol. Chem. 2009, 284, 12057−12070. (17) Gil, V.; MacLeod, A. J. The effects of pH on glucosinolate degradation by a thioglucoside glucohydrolase preparation. Phytochemistry 1980, 19, 2547−2551. (18) Agerbirk, N.; Olsen, C. E.; Sørensen, H. Initial and final products, nitriles, and ascorbigens produced in myrosinase-catalyzed hydrolysis of indole glucosinolates. J. Agric. Food Chem. 1998, 45, 1563−1571. (19) Mullaney, J. A.; Kelly, W. J.; McGhie, T. K.; Ansell, J.; Heyes, J. A. Lactic acid bacteria convert glucosinolates to nitriles efficiently yet differently from Enterobacteriaceae. J. Agric. Food Chem. 2013, 61, 3039−3046. (20) Daxenbichler, M. E.; VanEtten, C. H.; Brown, F. S.; Jones, Q. Oxazolidinethiones and volatile isothiocyanates in enzyme-treated seed meals from 65 species of Cruciferae. J. Agric. Food Chem. 1964, 12, 127−130. (21) Paik, I. K.; Robblee, A. R.; Clandinin, D. R. Products of the hydrolysis of rapeseed glucosinolates. Can. J. Anim. Sci. 1980, 60, 481− 493. 7374



Perspective

(42) Ghanayem, B. I.; Burka, L. T. Excretion and identification of methacrylonitrile in the bile of male F344 rats. Drug Metab. Dispos. 1996, 24, 390−394. (43) Brocker, E. R.; Benn, M. H. The intramolecular formation of epithioalkanenitriles from alkenylglucosinolates by Crambe abyssinica seed flour. Phytochemistry 1983, 22, 770−772. (44) Benn, M. Glucosinolates. Pure Appl. Chem. 1977, 49, 197−210. (45) Lüthy, J.; Benn, M. Cyanoepithioalkanes: some chemical and toxicological studies. In Natural Sulfur Compounds; Cavallini, D., Gaull, G. E., Zappia, V., Eds.; Plenum Press: New York, 1980; pp 381−389. (46) Brocker, E. R.; Benn, M. H.; Lüthy, J.; Von Däniken, A. Metabolism and distribution of 3,4-epithiobutanenitrile in the rat. Food Chem. Toxicol. 1984, 22, 227−232. (47) Fokin, A. V.; Kolomiets, A. F. The reactivity of epithiocompounds. Russ. Chem. Rev. 1976, 45, 25−42. (48) VanSteenhouse, J. L.; Fettman, M. J.; Gould, D. H. Sequential changes in hepatic and renal glutathione and development of renal karyomegaly in 1-cyano-3,4-epithiobutane toxicity in rats. Food Chem. Toxicol. 1989, 27, 731−739. (49) VanSteenhouse, J. L.; Prescott, J. S.; Barker, S. A. Identification of the 1-cyano-3,4-epithiobutane-derived urinary mercapturic acid nacetyl-s-(4-cyano-2-thio-1-butyl)-cysteine in male Fischer 344 rats. J. Appl. Toxicol. 2000, 20, 1−10. (50) VanSteenhouse, J. L.; Prescott, J. S.; Swenson, D. H. Protection from 1-cyano-3,4-epithiobutane nephrotoxicity by aminooxyacetic acid and effect on xenobiotic-metabolizing enzymes in male Fischer 344 rats. J. Appl. Toxicol. 1999, 19, 237−249. (51) Willhite, C. C.; Smith, R. P. The role of cyanide liberation in the acute toxicity of aliphatic nitriles. Toxicol. Appl. Pharmacol. 1981, 59, 589−602. (52) Tanii, H.; Hashimoto, K. Studies on the mechanism of acute toxicity of nitriles in mice. Arch. Toxicol. 1984, 55, 47−54. (53) Ahmed, A. E.; Farooqui, M. Y. H. Comparative toxicities of aliphatic nitriles. Toxicol. Lett. 1982, 12, 157−163. (54) Silver, E. H.; Kuttab, S. H.; Hasan, T.; Hassan, M. Structural considerations in the metabolism of nitriles to cyanide in vivo. Drug Metab. Dispos. 1982, 10, 495−498. (55) Duncan, A. J.; Milne, J. A. Effect of long-term intra-ruminal infusion of the glucosinolate metabolite allyl cyanide on the voluntary food intake and metabolism of lambs. J. Sci. Food Agric. 1992, 58, 9− 14. (56) Duncan, A. J.; Milne, J. A. Effects of oral administration of brassica secondary metabolites, allyl cyanide, allyl isothiocyanate and dimethyl disulphide, on the voluntary food intake and metabolism of sheep. Br. J. Nutr. 1993, 70, 631−645. (57) Niedoborski, T. E.; Klein, B. P.; Wallig, M. A. Rapid isolation and purification of 1-cyano-2-hydroxy-3-butene (crambene) from Crambe abyssinica seed meal using immiscible solvent extraction and high-performance liquid chromatography. J. Agric. Food Chem. 2001, 49, 3594−3599. (58) VanEtten, C. H.; Daxenbichler, M. E.; Schroeder, W.; Princen, L. H.; Perry, T. W. Tests for epi-progoitrin, derived nitriles, and goitrin in body tissues from cattle fed crambe meal. Can. J. Anim. Sci. 1977, 57, 75−80. (59) Westwood, C. T.; Mulcock, H. Nutritional evaluation of five species of forage brassica. Proc. N.Z. Grassland Assoc. 2012, 74, 31−38.

■

NOTE ADDED AFTER ASAP PUBLICATION The structures in Table 1 have been revised from the original posting of April 11, 2014. The correct version was posted July 8, 2014.

7375


Could Nitrile Derivatives of Turnip (Brassica rapa) Glucosinolates Be

Recommend Documents