630
Views
48
CrossRef citations to date
0
Altmetric
Review Article

Pharmacokinetics and pharmacodynamics of isothiocyanates

, , &
Pages 387-407 | Received 01 Oct 2010, Accepted 03 Mar 2011, Published online: 10 May 2011

References

  • Al Janobi, A. A., Mithen, R. F., Gasper, A. V., Shaw, P. N., Middleton, R. J., Ortori, C. A., et al. (2006). Quantitative measurement of sulforaphane, iberin, and their mercapturic acid pathway metabolites in human plasma and urine using liquid chromatography-tandem electrospray ionisation mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 844:223–234.
  • Baillie, T. A., Slatter, J. G. (1991). Glutathione: a vehicle for the transport of chemically reactive metabolites in vivo. Accounts Chem Res 24:264–270.
  • Bollard, M., Stribbling, S., Mitchell, S., Caldwell, J. (1997). The disposition of allyl isothiocyanate in the rat and mouse. Food Chem Toxicol 35:933–943.
  • Borghoff, S. J., Birnbaum, L. S. (1986). Age-related changes in the metabolism and excretion of allyl isothiocyanate. A model compound for glutathione conjugation. Drug Metab Dispos 14:417–422.
  • Breschi, M. C., Ducci, M., Tacca, M., Mazzanti, L., Giusiani, M., Poggi, G., et al. (1977). Distribution and fate of alpha-naphthl-isothiocyanate (ANIT) in the organs and body fluids of the rat. Arzneimittelforschung 27:122–126.
  • Bruggeman, I. M., Temmink, J. H., van Bladeren, P. J. (1986). Glutathione- and cysteine-mediated cytotoxicity of allyl and benzyl isothiocyanate. Toxicol Appl Pharmacol 83:349–359.
  • Brusewitz, G., Cameron, B. D., Chasseaud, L. F., Gorler, K., Hawkins, D. R., Koch, H., et al. (1977). The metabolism of benzyl isothiocyanate and its cysteine conjugate. Biochem J 162:99–107.
  • Capizzo, F., Roberts, R. J. (1970). Disposition of the hepatotoxin alpha-naphthylisothiocyanate (ANIT) in the rat. Toxicol Appl Pharmacol 17:262–271.
  • Capizzo, F., Roberts, R. J. (1971). -naphthylisothiocyanate (ANIT)-induced hepatotoxicity and disposition in various species. Toxicol Appl Pharmacol 19:176–187.
  • Carpenter-Deyo, L., Marchand, D. H., Jean, P. A., Roth, R. A., Reed, D. J. (1991). Involvement of glutathione in 1-naphthylisothiocyanate (ANIT) metabolism and toxicity to isolated hepatocytes. Biochem Pharmacol 42:2171–2180.
  • Cheung, K., Khor, T., Kong, A. N. (2009). Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation. Pharmaceut Res 26:224–231.
  • Chung, F. L., Jiao, D., Getahun, S. M., Yu, M. C. (1998). A urinary biomarker for uptake of dietary isothiocyanates in humans. Cancer Epidemiol Biomarkers Prev 7:103–108.
  • Chung, F. L., Morse, M. A., Eklind, K. I., Lewis, J. (1992). Quantitation of human uptake of the anticarcinogen phenethyl isothiocyanate after a watercress meal. Cancer Epidemiol Biomarkers Prev 1:383–388.
  • Conaway, C. C., Getahun S. M., Liebes, L. L., Pusateri, D. J., Topham, D. K. W., Botero-Omary, M., et al. (2000). Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli. Nutr Cancer 38:168–178.
  • Conaway, C. C., Jiao, D., Kohri, T., Liebes, L., Chung, F. L. (1999). Disposition and pharmacokinetics of phenethyl isothiocyanate and 6-phenylhexyl isothiocyanate in F344 rats. Drug Metab Dispos 27:13–20.
  • Conaway, C. C., Jiao, D., Liebes, L. L., Chung, F. L. (1998). Pharmacokinetics and metabolism of phenethyl isothiocyanate and 6-phenylhexyl isothiocyanate in F344 rats [Abstract 119]. Proc Am Assoc Cancer Res 39:18.
  • Conaway, C. C., Krzeminski, J., Amin, S., Chung, F. L. (2001). Decomposition rates of isothiocyanate conjugates determine their activity as inhibitors of cytochrome p450 enzymes. Chem Res Toxicol 14:1170–1176.
  • Conaway, C. C., Yang, Y. M., Chung, F. L. (2002). Isothiocyanates as cancer chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr Drug Metab 3:233–255.
  • Conrad, A., Kolberg, T., Engels, I., Frank, U. (2006). In vitro study to evaluate the antibacterial activity of a combination of the haulm of nasturtium (Tropaeoli majoris herba) and of the roots of horseradish (Armoraciae rusticanae radix). Arzneimittelforschung 56:842–849.
  • Cornblatt, B. S., Ye, L., Dinkova-Kostova, A. T., Erb, M., Fahey, J. W., Singh, N. K., et al. (2007). Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis 28:1485–1490.
  • Dey, M., Ribnicky, D., Kurmukov, A. G., Raskin, I. (2006). In vitro and in vivo anti-inflammatory activity of a seed preparation containing phenethylisothiocyanate. J Pharmacol Exp Ther 317:326–333.
  • Dietrich, C. G., Ottenhoff, R., de Waart, D. R., Elferink, R. P. J. O. (2001). Role of MRP2 and GSH in intrahepatic cycling of toxins. Toxicology 167:73–81.
  • Drobnica, L., Augustin, J. (1965). Reaction of isothiocyanates with amino acids, peptides and proteins. I. Kinetics of reaction of aromatic isothiocyanates with glycine. Collection Czech Chem Commun 30:99–104.
  • Drobnica, L., Kristian, P., Augustin, J. (1977). The chemistry of the -NCS group. In: Patai, S. (Ed.), The chemistry of cyanates and their thiol derivatives, part 2 ( pp. 1003–1221). New York: John Wiley & Sons.
  • Duncan, A. J., Rabot, S., NugonBaudon, L. (1997). Urinary mercapturic acids as markers for the determination of isothiocyanate release from glucosinolates in rats fed a cauliflower diet. J Sci Food Agric 73:214–220.
  • Eklind, K. I., Morse, M. A., Chung, F. L. (1990). Distribution and metabolism of the natural anticarcinogen phenethyl isothiocyanate in A/J mice. Carcinogenesis 11:2033–2036.
  • Gasper, A. V., Al-Janobi, A., Smith, J. A., Bacon, J. R., Fortun, P., Atherton, C., et al. (2005). Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr 82:1283–1291.
  • Getahun, S. M., Chung, F. L. (1999). Conversion of glucosinolates to isothiocyanates in humans after ingestion of cooked watercress. Cancer Epidemiol Biomarkers Prev 8:447–451.
  • Goosen, T. C., Mills, D. E., Hollenberg, P. F. (2001). Effects of benzyl isothiocyanate on rat and human cytochromes P450: identification of metabolites formed by P450 2B1. J Pharmacol Exp Ther 296:198–206.
  • Gorler, K., Krumbiegel, G., Mennicke, W. H., Siehl, H. U. (1982). The metabolism of benzyl isothiocyanate and its cysteine conjugate in guinea-pigs and rabbits. Xenobiotica 12:535–542.
  • Halbeisen, T. (1954). Untersuchungen uber die antibiotischen wirkstoffe von tropaeolum maius (kapuzinerkresse). Naturwissenschaften 41:378–379.
  • Hanlon, N., Coldham, N., Gielbert, A., Kuhnert, N., Sauer, M. J., Kingi, L. J., et al. (2008). Absolute bioavailability and dose-dependent pharmacokinetic behaviour of dietary doses of the chemopreventive isothiocyanate sulforaphane in rat. Br J Nutr 99:559–564.
  • Hecht, S. S. (1999). Chemoprevention of cancer by isothiocyanates, modifiers of carcinogen metabolism. J Nutr 129:S768–S774
  • Hecht, S. S., Carmella, S. G., Murphy, S. E. (1999). Effects of watercress consumption on urinary metabolites of nicotine in smokers. Cancer Epidemiol Biomarkers Prev 8:907–913.
  • Holst, B., Williamson, G. (2004). A critical review of the bioavailability of glucosinolates and related compounds. Nat Prod Rep 21:425–447.
  • Hu, K., Morris, M. E. (2003). Determination of alpha-naphthylisothiocyanate and metabolites alpha-naphthylamine and alpha-naphthylisocyanate in rat plasma and urine by high-performance liquid chromatography. J Chromatogr B Anal Technol Biomed Life Sci 788:17–28.
  • Hu, K., Morris, M. E. (2004). Effects of benzyl-, phenethyl-, and alpha-naphthyl isothiocyanates on P-glycoprotein- and MRP1-mediated transport. J Pharm Sci 93:1901–1911.
  • Hu, K., Morris, M. E. (2005). Pharmacokinetics of alpha-naphthyl isothiocyanate in rats. J Pharmaceut Sci 94:2441–2451.
  • Hu, R., Hebbar, V., Kim, B. R., Chen, C., Winnik, B., Buckley, B., et al. (2004). In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat. J Pharmacol Exp Ther 310:263–271.
  • Hwang, E. S., Jeffery, E. H. (2003). Evaluation of urinary N-acetyl cysteinyl allyl isothiocyanate as a biomarker for intake and bioactivity of Brussels sprouts. Food Chem Toxicol 41:1817–1825.
  • Ioannou, Y. M., Burka, L. T., Matthews, H. B. (1984). Allyl isothiocyanate: comparative disposition in rats and mice. Toxicol Appl Pharmacol 75:173–181.
  • Jakubikova, J., Bao, Y., Sedlak, J. (2005). Isothiocyanates induce cell cycle arrest, apoptosis and mitochondrial potential depolarization in HL-60 and multidrug-resistant cell lines. Anticancer Res 25:3375–3386.
  • Ji, Y., Kuo, Y. S., Morris, M. E. (2005). Pharmacokinetics of dietary phenethyl isothiocyanate in rats. Pharmaceut Res 22:1658–1666.
  • Ji, Y., Morris, M. E. (2003). Determination of phenethyl isothiocyanate in human plasma and urine by ammonia derivatization and liquid chromatography-tandem mass spectrometry. Anal Biochem 323:39–47.
  • Jiang, Z. T., Zhang, Q. F., Tian, H. L., Li, R. (2006). The reaction of allyl isothiocyanate with hydroxyl/water and beta-cyclodextrin using ultraviolet spectrometry. Food Technol Biotechnol 44:423–427.
  • Jiao, D., Eklind, K. I., Choi, C. I., Desai, D. H., Amin, S. G., Chung, F. L. (1994a). Structure-activity relationships of isothiocyanates as mechanism-based inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice. Cancer Res 54:4327–4333.
  • Jiao, D., Ho, C. T., Foiles, P., Chung, F. L. (1994b). Identification and quantification of the N-acetylcysteine conjugate of allyl isothiocyanate in human urine after ingestion of mustard. Cancer Epidemiol Biomarkers Prev 3:487–492.
  • Juge, N., Mithen, R. F., Traka, M. (2007). Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci 64:1105–1127.
  • Kassahun, K., Davis, M., Hu, P., Martin, B., Baillie, T. (1997). Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat: identification of phase I metabolites and glutathione conjugates. Chem Res Toxicol 10:1228–1233.
  • Kassie, F., Pool-Zobel, B., Parzefall, W., Knasmuller, S. (1999). Genotoxic effects of benzyl isothiocyanate, a natural chemopreventive agent. Mutagenesis 14:595–604.
  • Kolm, R. H., Danielson, U. H., Zhang, Y., Talalay, P., Mannervik, B. (1995). Isothiocyanates as substrates for human glutathione transferases: structure-activity studies. Biochem J 311(Pt 2):453–459.
  • Kristensen, M., Krogholm, K. S., Frederiksen, H., Bugel, S. H., Rasmussen, S. E. (2007a). Urinary excretion of total isothiocyanates from cruciferous vegetables shows high dose-response relationship and may be a useful biomarker for isothiocyanate exposure. Eur J Nutr 46:377–382.
  • Kristensen, M., Krogholm, K. S., Frederiksen, H., Duus, F., Cornett, C., Bugel, S. H., et al. (2007b). Improved synthesis methods of standards used for quantitative determination of total isothiocyanates from broccoli in human urine. J Chromatogr B Anal Technol Biomed Life Sci 852:229–234.
  • Kroll, J., Rawel, H., Krock, R., Proll, J., Schnaak, W. (1994). Interactions of isothiocyanates with egg-white proteins. Nahrung 38:53–60.
  • Lamy, E., Mersch-Sundermann, V. (2009). MTBITC mediates cell cycle arrest and apoptosis induction in human HepG2 cells despite its rapid degradation kinetics in the in vitro model. Environ Mol Mutagen 50:190–200.
  • Lee, M. S. (1992). Oxidative conversion by rat liver microsomes of 2-naphthyl isothiocyanate to 2-naphthyl isocyanate, a genotoxicant. Chem Res Toxicol 5:791–796.
  • Lee, M. S. (1994). Oxidative conversion of isothiocyanates to isocyanates by rat liver. Environ Health Perspect 102(Suppl 6):115–118.
  • Lee, M. S. (1996). Enzyme induction and comparative oxidative desulfuration of isothiocyanates to isocyanates. Chem Res Toxicol 9:1072–1078.
  • Li, Y., Yousef, I. M., Plaa, G. L. (1995). 1-naphthyl isocyanate and 1-naphthylamine as metabolites of 1-naphthylisothiocyanate. Liver 15:271–275.
  • Liebes, L., Conaway, C. C., Hochster, H., Mendoza, S., Hecht, S. S., Crowell, J., et al. (2001). High-performance liquid chromatography-based determination of total isothiocyanate levels in human plasma: application to studies with 2-phenethyl isothiocyanate. Anal Biochem 291:279–289.
  • Mansoor, M. A., Svardal, A. M., Ueland, P. M. (1992). Determination of the in vivo redox status of cysteine, cysteinylglycine, homocysteine, and glutathione in human plasma. Anal Biochem 200:218–229.
  • Mennicke, W. H., Gorler, K., Krumbiegel, G. (1983). Metabolism of some naturally occurring isothiocyanates in the rat. Xenobiotica 13:203–207.
  • Mennicke, W. H., Gorler, K., Krumbiegel, G., Lorenz, D., Rittmann, N. (1988). Studies on the metabolism and excretion of benzyl isothiocyanate in man. Xenobiotica 18:441–447.
  • Mennicke, W. H., Kral, T., Krumbiegel, G., Rittmann, N. (1987). Determination of N-acetyl-S-(N-alkylthiocarbamoyl)-<SC>L<SC/>-cysteine, a principal metabolite of alkyl isothiocyanates, in rat urine. J Chromatogr 414:19–24.
  • Mennicke, W. H., Krumbiegel, G., Gorler, K. (1978). Metabolism of isothiocyanates in rats. Naunyn Schmiedebergs Arch Pharmacol (Suppl) 302:R13.
  • Meyer, D. J., Crease, D. J., Ketterer, B. (1995). Forward and reverse catalysis and product sequestration by human glutathione S-transferases in the reaction of GSH with dietary aralkyl isothiocyanates. Biochem J 306(Pt 2):565–569.
  • Mi, L., Wang, X., Govind, S., Hood, B. L., Veenstra, T. D., Conrads, T. P., et al. (2007). The role of protein binding in induction of apoptosis by phenethyl isothiocyanate and sulforaphane in human non-small lung cancer cells. Cancer Res 67:6409–6416.
  • Moldeus, P., Jones, D. P., Ormstad, K., Orrenius, S. (1978). Formation and metabolism of A glutathione-S-conjugate in isolated rat-liver and kidney cells. Biochem Biophys Res Commun 83:195–200.
  • Munday, R., Mhawech-Fauceglia, P., Munday, C. M., Paonessa, J. D., Tang, L., Munday, J. S., et al. (2008). Inhibition of urinary bladder carcinogenesis by broccoli sprouts. Cancer Res 68:1593–1600.
  • Munday, R., Zhang, Y., Fahey, J. W., Jobson, H. E., Munday, C. M., Li, J., et al. (2006). Evaluation of isothiocyanates as potent inducers of carcinogen-detoxifying enzymes in the urinary bladder: critical nature of in vivo bioassay. Nutr Cancer 54:223–231.
  • Murthy, N. V. K. K., Rao, A. G. A., Rao, M. S. N. (1986). A spectroscopic study of the interaction of allylisothiocyanate with mustard 12S protein. Int J Pept Prot Res 28:462–467.
  • Muztar, A. J., Huque, T., Ahmad, P., Slinger, S. J. (1979). Effect of allyl isothiocyanate on plasma and urinary concentrations of some biochemical entities in the rat. Can J Physiol Pharmacol 57:504–509.
  • Nakamura, T., Kawai, Y., Kitamoto, N., Osawa, T., Kato, Y. (2009). Covalent modification of lysine residues by allyl isothiocyanate in physiological conditions: plausible transformation of isothiocyanate from thiol to amine. Chem Res Toxicol 22:536–542.
  • NCI, D.C.P.C. (1996). Clinical development plan: phenethyl isothiocyanate. J Cell Biochem (Suppl) 26:149–157.
  • Oginsky, E. L., Stein, A. E., Greer, M. A. (1965). Myrosinase activity in bacteria as demonstrated by conversion of progoitrin to goitrin. Proc Soc Exp Biol Med 119:360–364.
  • Ohta, Y., Takatani, K., Kawakishi, S. (1995). Decomposition rate of allyl isothiocyanate in aqueous-solution. Biosci Biotechnol Biochem 59:102–103.
  • Parola, M., Cheeseman, K. H., Biocca, M. E., Dianzani, M. U., Slater, T. F. (1990). Biochemical studies on bile duct epithelial cells isolated from rat liver. J Hepatol 10:341–345.
  • Petri, N., Tannergren, C., Holst, B., Mellon, F. A., Bao, Y. P., Plumb, G. W., et al. (2003). Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo. Drug Metab Dispos 31:805–813.
  • Rabot, S., Guerin, C., NugonBaudon, L., Szylit, O. (1995) Glucosinolate degradation by bacterial strains isotlated from a human intestinal microflora. Proc 9th Int Rapeseed Congress 1:212–214.
  • Riedl, M. A., Saxon, A., az-Sanchez, D. (2009). Oral sulforaphane increases phase II antioxidant enzymes in the human upper airway. Clin Immunol 130:244–251.
  • Rouzaud, G., Rabot, S., Ratcliffe, B., Duncan, A. J. (2003). Influence of plant and bacterial myrosinase activity on the metabolic fate of glucosinolates in gnotobiotic rats. Br J Nutr 90:395–404.
  • Rouzaud, G., Young, S. A., Duncan, A. J. (2004). Hydrolysis of glucosinolates to isothiocyanates after ingestion of raw or microwaved cabbage by human volunteers. Cancer Epidemiol Biomarkers Prev 13:125–131.
  • Shapiro, T. A., Fahey, J. W., Dinkova-Kostova, A. T., Holtzclaw, W. D., Stephenson, K. K., Wade, K. L., et al. (2006). Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study. Nutr Cancer 55:53–62.
  • Shapiro, T. A., Fahey, J. W., Wade, K. L., Stephenson, K. K., Talalay, P. (1998). Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol Biomarkers Prev 7:1091–1100.
  • Shapiro, T. A., Fahey, J. W., Wade, K. L., Stephenson, K. K., Talalay, P. (2001). Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. Cancer Epidemiol Biomarkers Prev 10:501–508.
  • Sies, H., Wahllander, A., Waydhas, C., Soboll, S., Hoberle, D. (1980). Functions of intracellular glutathione in hepatic hydroperoxide and drug metabolism and the role of extracellular glutathione. Adv Enzyme Regul 18:303–320.
  • Sommerlade, R., Perihan, E., Harun, P. (2006). Gas phase reaction of selected isothiocyanates with OH radicals using a smog chamber-mass analyzer system. Atmos Environ 40:3306–3315.
  • Telang, U., Ji, Y., Morris, M. E. (2009). ABC transporters and isothiocyanates: potential for pharmacokinetic diet-drug interactions. Biopharm Drug Dispos 30:335–344.
  • Tseng, E., Scott-Ramsay, E. A., Morris, M. E. (2004). Dietary organic isothiocyanates are cytotoxic in human breast cancer MCF-7 and mammary epithelial MCF-12A cell lines. Exp Biol Med 229:835–842.
  • Vermeulen, M., Van den Berg, R., Freidig, A. P., van Bladeren, P. J., Vaes, W. H. J. (2006). Association between consumption of cruciferous vegetables and condiments and excretion in urine of isothiocyanate mercapturic acids. J Agric Food Chem 54:5350–5358.
  • Vermeulen, M., van Rooijen, H. J. M., Vaes, W. H. J. (2003). Analysis of isothiocyanate mercapturic acids in urine: a biomarker for cruciferous vegetable intake. J Agric Food Chem 51:3554–3559.
  • Xu, K., Thornalley, P. J. (2000). Studies on the mechanism of the inhibition of human leukaemia cell growth by dietary isothiocyanates and their cysteine adducts in vitro. Biochem Pharmacol 60:221–231.
  • Xu, K., Thornalley, P. J. (2001). Involvement of glutathione metabolism in the cytotoxicity of the phenethyl isothiocyanate and its cysteine conjugate to human leukaemia cells in vitro. Biochem Pharmacol 61:165–177.
  • Ye, L., Dinkova-Kostova, A. T., Wade, K. L., Zhang, Y., Shapiro, T. A., Talalay, P. (2002). Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes, and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans. Clin Chim Acta 316:43–53.
  • Zhang, Y. (2000). Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells. Carcinogenesis 21:1175–1182.
  • Zhang, Y. (2001). Molecular mechanism of rapid cellular accumulation of anticarcinogenic isothiocyanates. Carcinogenesis 22:425–431.
  • Zhang, Y., Callaway, E. C. (2002). High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem J 364:301–307.
  • Zhang, Y., Cho, C. G., Posner, G. H., Talalay, P. (1992). Spectroscopic quantitation of organic isothiocyanates by cyclocondensation with vicinal dithiols. Anal Biochem 205:100–107.
  • Zhang, Y., Kolm, R. H., Mannervik, B., Talalay, P. (1995). Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. Biochem Biophys Res Commun 206:748–755.
  • Zhang, Y., Talalay, P. (1998). Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic phase 2 enzymes. Cancer Res 58:4632–4639.
  • Zhang, Y., Wade, K. L., Prestera, T., Talalay, P. (1996). Quantitative determination of isothiocyanates, dithiocarbamates, carbon disulfide, and related thiocarbonyl compounds by cyclocondensation with 1,2-benzenedithiol. Anal Biochem 239:160–167.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.