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Computational Toxicology pp 367–394Cite as

Toxicity Potential of Nutraceuticals

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1800))

Abstract

By the turn of the twenty-first century, the use of nutraceuticals became increasingly popular in both humans and animals due to their easy access, cost-effectiveness, and tolerability with a wide margin of safety. While some nutraceuticals are safe, others have a toxic potential. For a large number of nutraceuticals, no toxicity/safety data are available due to a lack of pharmacological/toxicological studies. The safety of some nutraceuticals can be compromised via contamination with toxic plants, metals, mycotoxins, pesticides, fertilizers, drugs of abuse, etc. Knowledge of pharmacokinetic/toxicokinetic studies appears to play a pivotal role in safety and toxicity assessment of nutraceuticals. Interaction studies are essential to determine efficacy, safety, and toxicity when nutraceuticals and therapeutic drugs are used concomitantly. This chapter describes various aspects of nutraceuticals, particularly their toxic potential, and the factors influencing their safety.

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References

  1. Pandey M, Verma RK, Saraf SA (2010) Nutraceuticals: new era of medicine and health. Asian J Pharmaceut. Clin Res 3:11–15

    Google Scholar 

  2. Gupta RC (ed) (2016) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam. 1022 pages

    Google Scholar 

  3. Gil F, Hernández AF, Martín-Domingo MC (2016) Toxic contamination of nutraceuticals and food ingredients. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 825–837

    Chapter  Google Scholar 

  4. FDA (1994) Dietary supplement health and education act of 1994. Congress, Pub. L. www.fda.gov/DietarySupplement/default.htm

  5. NTP (2010) Toxicology and carcinogenesis studies of goldenseal root powder (Hydrastis canadensis) in F344/N rats and B6C3F1 mice (feed studies). Natl Toxicol Program Tech Rep Ser 562:1–188

    Google Scholar 

  6. Gurley BJ, Gardner SF, Hubbard MA et al (2005) In vivo effects of goldenseal, kava kava, black kohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 77:415–426

    Article  PubMed  CAS  Google Scholar 

  7. Zhang Z, Mei N, Chen S et al (2016) Assessment of genotoxic effects of selected herbal dietary supplements. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 883–892

    Chapter  Google Scholar 

  8. Heinonen T, Wilhelm G (2015) Cross matching observations on toxicological and clinical data for the assessment of tolerability and safety of Ginkgo biloba leaf extract. Toxicology 327:95–115

    Article  PubMed  CAS  Google Scholar 

  9. Bent S, Goldberg H, Padula A et al (2005) Spontaneous bleeding associated with Ginkgo biloba; a case report and systematic review of the literature. J Gen Intern Med 20:657–661

    Article  PubMed  PubMed Central  Google Scholar 

  10. Posadzki P, Watson L, Ernst E (2012) Herb-drug interactions: an overview of systematic reviews. Br J Clin Pharmacol 75:603–618

    Article  CAS  Google Scholar 

  11. Diamond B, Baily M (2013) Ginkgo biloba; indications, mechanisms and safety. Psychiatr Clin North Am 36:73–78

    Article  PubMed  Google Scholar 

  12. Dziwenka M, Coppock RW (2016) Ginkgo biloba. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 681–691

    Chapter  Google Scholar 

  13. Ude C, Schubert-Zsilavecz M, Wurglics M (2013) Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients. Clin Pharmacokinet 52:727–749

    Article  PubMed  CAS  Google Scholar 

  14. NTP (2013) Toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS No. 90045-36-6) in F344/N rats and B6C3F1/N mice (Gavage studies). Nat Toxicol Program Tech Report Ser 578:1–183

    Google Scholar 

  15. Coppock RW, Dziwenka M (2016) Green tea extract. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 633–652

    Chapter  Google Scholar 

  16. Kapetanovic IM, Crowell JA, Krishnaraj R et al (2009) Exposure and toxicity of green tea polyphenols in fasted and nonfasted dogs. Toxicology 260:28–38

    Article  PubMed  CAS  Google Scholar 

  17. Lambert JD, Kennett MJ, Sang S et al (2010) Hepatotoxicity of high oral dose (-)- epigallocatechin-3-gallate in mice. Food Chem Toxicol 48:409–416

    Article  PubMed  CAS  Google Scholar 

  18. Chandra AK, Choudhury SR, De N et al (2011) Effect of green tea (Camellia sinensis) extract on morphological and functional changes in adult male gonads of albino rats. Indian J Exp Biol 49:689–697

    PubMed  CAS  Google Scholar 

  19. Shimizu M, Shirakami Y, Sakai H et al (2015) Chemopreventive potential of green tea catechins in hepatocellular carcinoma. Int J Mol Sci 16:6124–6139

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Ogunleye AA, Xue F, Michels KB (2010) Green tea consumption and breast cancer risk or recurrence: a meta-analysis. Breast Cancer Res Treat 119:477–484

    Article  PubMed  Google Scholar 

  21. Abd El-Aty AM, Choi JH, Rahman MM et al (2014) Residues and contaminants in tea and tea infusions: a review. Food Addit Contam Part A 31:1794–1804

    Article  CAS  Google Scholar 

  22. Wang J, Cheung W, Leung D (2014) Determination of pesticide residue transfer rates (percent) from dried tea leaves to brewed tea. J Agric Food Chem 62:966–983

    Article  PubMed  CAS  Google Scholar 

  23. Garg SK (2016) Green coffee bean. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 653–667

    Chapter  Google Scholar 

  24. Fredholm BB, Bättig K, Holmén J et al (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133

    PubMed  CAS  Google Scholar 

  25. Rudolph T, Knudsen K (2010) A case of fatal caffeine poisoning. Acta Anesth Scand 54:521–523

    Article  CAS  Google Scholar 

  26. Campana C, Griffin PL, Simon EL (2014) Caffeine overdose resulting in severe rhabdomyolysis and acute renal failure. Am J Emerg Med 32:111.e3–111.e4

    Article  Google Scholar 

  27. Menezes FP, Da Silva RS (2017) Caffeine. In: Gupta RC (ed) Reproductive and developmental toxicology, 2nd edn. Academic Press/Elsevier, Amsterdam, pp 399–411

    Chapter  Google Scholar 

  28. Roberts A (2016) Caffeine: an evaluation of the safety database. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 417–434

    Chapter  Google Scholar 

  29. EFSA (2015) Scientific opinion on the safety of caffeine. EFSA J 13(5):1–120

    Google Scholar 

  30. Raina R, Mondhe DM, Malik JK, Gupta RC (2016) Garcinia cambogia. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 669–680

    Chapter  Google Scholar 

  31. Kayode OA, Jimoh Olusegun R, Adesanya Olamide A et al (2007) Effects of crude ethanolic extract of Garcinia cambogia on the reproductive system of male Wistar rats (Rattus norwegicus). Afr J Biotechnol 6:1236–1238

    Google Scholar 

  32. Kim YJ, Choi MS, Park YB et al (2013) Garcinia cambogia attenuates diet induced adiposity but exacerbates hepatic collagen accumulation and inflammation. World J Gastroenterol 19:4689–4701

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dara L, Hewett J, Lim JK (2008) Hydroxycut hepatotoxicity: a case series and review of liver toxicity from herbal weight loss supplements. World J Gastroenterol 14:6999–7004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Sharma T, Wong L, Tsai N et al (2010) Hydroxycut® (herbal weight loss supplement) induced hepatotoxicity: a case report and review of literature. Hawaii Med J 69:188–190

    PubMed  PubMed Central  Google Scholar 

  35. Kaswala DH, Shah S, Patel N et al (2014) Hydroxycut-induced liver toxicity. Ann Med Health Sci Res 4:143–145

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lopez AM, Kornegay J, Hendrickson RG (2014) Serotonin toxicity associated with Garcinia cambogia over-the-counter supplement. J Med Toxicol 10:399–401

    Article  PubMed  PubMed Central  Google Scholar 

  37. Zhou P, Gross S, Liu J-H et al (2010) Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathways. FASEB J 24:4722–4732

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Coppock RW, Dziwenka M (2016) St. John’s wort. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 619–631

    Chapter  Google Scholar 

  39. Becker LC, Bergfeld WF, Belsito DV et al (2014) Amended safety assessment of Hypericum perforatum-derived ingredients as used in cosmetics. Int J Toxicol 33(3 suppl):5S–23S

    Article  PubMed  Google Scholar 

  40. Brown TM (2000) Acute St. John’s wort toxicity. Am J Emerg Med 18:231–232

    Article  PubMed  Google Scholar 

  41. Lampri ES, Ioachim E, Harissis H et al (2014) Pleomorphic hepatocellular carcinoma following consumption of Hypericum perforatum in alcoholic cirrhosis. Wolrd J Gastroenterol 20:2113–2116

    Google Scholar 

  42. Demiroglu YZ, Yeter TT, Boga C et al (2005) Bone marrow necrosis: a rare complication of herbal treatment with Hypericum perforatum (St. John’s Wort). Acta Med Austriaca 48:91–94

    Google Scholar 

  43. Gupta RC, Chang D, Nammi S et al (2017) Interactions between antidiabetic drugs and herbs: an overview of mechanisms of action and clinical implications. Diabetol Metab Syndr 9:59

    Article  PubMed  PubMed Central  Google Scholar 

  44. Joseph B, Jini D (2013) Antidiabetic effects of Momordica charantia (bitter melon) and its medicinal potency. Asian Pac J Trop Dis 3(2):93–102

    Article  PubMed Central  Google Scholar 

  45. Ojewole JA, Adewole SO, Olayiwola G (2006) Hypoglycemic and hypotensive effects of Momordica charantia Linn (Cucurbitaceae) whole-plant aqueous extract in rats. Cardiovasc J South Afr 17:227–232

    Google Scholar 

  46. Chan N, Li S, Perez E (2016) Interactions between Chinese nutraceuticals and western medicines. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 875–882

    Chapter  Google Scholar 

  47. Bitter Mellon (2013) Bitter Mellon. http://www.zmescience.com. Accessed 20 March 2013

  48. Gupta VK, Malhotra S (2012) Pharmacological attribute of Aloe vera: revalidation through experimental and clinical studies. AYU 33:193–196. http://www.ayujournal.org/text.asp?2012/33/2/193/105237

    Article  PubMed  PubMed Central  Google Scholar 

  49. Choudhary M, Kochhar A, Sangha J (2014) Hypoglycemic and hypolipidemic effect of Aloe vera L. in non-insulin dependent diabetics. J Food Sci Technol 51:90–96

    Article  PubMed  CAS  Google Scholar 

  50. IARC (2006) IARC Monograph on the evaluation of carcinogenic risks to humans. Preamble. http://monographs.iarc.fr/ENG/Preamble/CurrentPreamble.pdf

  51. Proposition 65 (2015) Chemicals listed effective December 4, 2015 as Known to the State of California to cause cancer: Aloe vera, non-decolorized whole leaf extract and goldenseal root powder. US Office of Environmental Health Hazard Assessment. 4 December 2015

    Google Scholar 

  52. Nesslany F, Simar-Meintieres S, Ficheux H et al (2009) Aloe-emodin-induced DNA fragmentation in the mouse in vivo comet assay. Mutat Res 678:13–19

    Article  PubMed  CAS  Google Scholar 

  53. Hilmas CJ, Fabricant DS (2014) Biomarkers of toxicity for dietary ingredients contained in dietary supplements. In: Gupta RC (ed) Biomarkers in toxicology. Academic Press/Elsevier, Amsterdam, pp 609–627

    Chapter  Google Scholar 

  54. Means C (1999) Ma huang: all natural but not always innocuous. Vet Med 94:511–512

    Google Scholar 

  55. Means C (2005) Decongestants. In: Plumlee K (ed) Clinical veterinary toxicology. Mosby, St. Louis, MO, pp 309–311

    Google Scholar 

  56. Ooms TG, Khan S (2001) Suspected caffeine and ephedrine toxicosis resulting from ingestion of an herbal supplement containing guarana and ma huang in dogs: 47 cases (1997-1999). J Am Vet Med Assoc 218:225–229

    Article  PubMed  CAS  Google Scholar 

  57. Andraws R, Chawla P, Brown DL (2005) Cardiovascular effects of ephedra alkaloids: a comprehensive review. Prog Cardiovasc Dis 47:217–225

    Article  PubMed  CAS  Google Scholar 

  58. Flanagan CM, Kaesberg JL, Mitchell ES et al (2010) Coronary artery and thrombosis following chronic ephedra use. Int J Cardiol 139(1):e11–e13

    Article  PubMed  Google Scholar 

  59. Nyska A, Murphy E, Foley JE et al (2005) Acute hemorrhagic myocardial necrosis and sudden death of rats exposed to a combination of ephedrine and caffeine. Toxicol Sci 83:388–396

    Article  PubMed  CAS  Google Scholar 

  60. Dunnick JK, Kissling G, Gerken DK et al (2007) Cardiotoxicity of Ma Huang/caffeine in a rodent model system. Toxicol Pathol 35:657–666

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Sullivan JB, Rumack BH, Thomas H et al (1979) Pennyroyal oil poisoning and hepatotoxicity. JAMA 242:2873–2874

    Article  PubMed  Google Scholar 

  62. Anderson IB, Mullen WH, Mecker JE et al (1996) Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med 124:726–734

    Article  PubMed  CAS  Google Scholar 

  63. Torres LRDO, de Santana FC, Torres-Leal FL et al (2016) Pequi (Caryocar brasiliense Camb) almond oil attenuates carbon tetrachloride-induced acute hepatic injury in rats: antioxidant and anti-inflammatory effects. Food Chem Toxicol 97:206–216

    Article  CAS  Google Scholar 

  64. Traesel GK, Menegati SELT, dos Santos AC et al (2016) Oral acute and subchronic toxicity studies of the oil extracted from Pequi (Caryocar brasiliense, Camb) pulp in rats. Food Chem Toxicol 97:224–231

    Article  PubMed  CAS  Google Scholar 

  65. Ang-Lee MK, Moss J, Chen-Su Y (2001) Herbal medicines and perioperative care. Review. JAMA 286(2):208–216

    Article  PubMed  CAS  Google Scholar 

  66. Chan K (2003) Some aspects of toxic contaminants in herbal medicines. Chemosphere 52(9):1361–1371

    Article  PubMed  CAS  Google Scholar 

  67. Jordan SA, Cunningham DG, Marles RJ (2010) Assessment of herbal products: challenges, and opportunities to increase the knowledge base for safety assessment. Toxicol Appl Pharmacol 243:198–216

    Article  PubMed  CAS  Google Scholar 

  68. Shi S, Klotz U (2012) Drug interactions with herbal medicines. Clin Pharm 51:77–104

    Article  CAS  Google Scholar 

  69. Guo B, Wang M, Liu Y et al (2015) Wide-scope screening of illegal adulterants in dietary and herbal supplements via rapid polarity-switching and multistage accurate mass confirmation using an LC-IT/TOF hybrid instrument. J Agric Food Chem 63:6954–6967

    Article  PubMed  CAS  Google Scholar 

  70. Panter KE, Welch KD, Gardner DR (2014) Poisonous plants: biomarkers for diagnosis. In: Gupta RC (ed) Biomarkers in toxicology. Academic Press/Elsevier, Amsterdam, pp 563–589

    Chapter  Google Scholar 

  71. Merz K-H, Schrenk D (2016) Interim relative potency factors for the toxicological risk assessment of pyrrolizidine alkaloids in food and herbal medicines. Toxicol Lett 263:44–57

    Article  PubMed  CAS  Google Scholar 

  72. Preliasco M, Gardner D, Moraes J et al (2017) Senecio grisebachii Baker: Pyrrolizidine alkaloids and experimental poisoning in calves. Toxicon 133:66–73

    Article  CAS  Google Scholar 

  73. Wang Y, Xiang L, Yi X et al (2017) Potential anti-inflammatory steroidal saponins from the barriers of Solanum nigrum (European black nightshade). J Agric Food Chem 65:4262–4272

    Article  PubMed  CAS  Google Scholar 

  74. Winship KA (1991) Toxicity of comfrey. Adverse Drug React Toxicol Rev 10:47–59

    PubMed  CAS  Google Scholar 

  75. Fu PP, Xia QS, He XB et al (2017) Detection of pyrrolizidine alkaloid DNA adducts in livers of cattle poisoned with Heliotropium europaeum. Chem Res Toxicol 30:851–858

    Article  PubMed  CAS  Google Scholar 

  76. Yang XJ, Li WW, Sun Y et al (2017) Comparative study of hepatotoxicity of pyrrolizidine alkaloids retrorsine and monocrotaline. Chem Res Toxicol 30:532–539

    Article  PubMed  CAS  Google Scholar 

  77. Zhu L, Xue J, Xia Q et al (2017) The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice. Genotox Carcinogen 91:949–965

    CAS  Google Scholar 

  78. Meena AK, Bansal P, Kumar S et al (2010) Estimation of heavy metals in commonly used medicinal plants: a market basket survey. Environ Monit Assess 170:657–660

    Article  PubMed  CAS  Google Scholar 

  79. Harris ES, Cao S, Littlefield BA et al (2011) Heavy metal and pesticide content in commonly prescribed individual raw Chinese herbal medicines. Sci Total Environ 409:4297–4305

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Rao MM, Meena AK et al (2011) Detection of toxic heavy metals and pesticide residue in herbal plants which are commonly used in the herbal formulations. Environ Monit Assess 181:267–271

    Article  PubMed  CAS  Google Scholar 

  81. Sarma H, Deka S, Deka H et al (2011) Accumulation of heavy metals in selected medicinal plants. Rev Environ Contam Toxicol 214:63–86

    PubMed  CAS  Google Scholar 

  82. Mehta V, Midha V, Mahajan R et al (2017) Lead intoxication due to Ayurvedic medications as a cause of abdominal pain in adults. Clin Toxicol 55:97–101

    Article  CAS  Google Scholar 

  83. Flora SJS, Agrawal S (2017) Arsenic, cadmium, and lead. In: Gupta RC (ed) Reproductive and developmental toxicology. Academic Press/Elsevier, Amsterdam, pp 537–566

    Chapter  Google Scholar 

  84. Flora SJS (2014) Metals. In: Gupta RC (ed) Biomarkers in toxicology. Academic Press/Elsevier, Amsterdam, pp 485–519

    Chapter  Google Scholar 

  85. Bridges CC, Zalpus RK (2017) The aging kidney and the nephrotoxic effects of mercury. J Toxicol Environ Health Part B 20:55–80

    Article  CAS  Google Scholar 

  86. Gasser U, Klier B, Kuhn AV et al (2009) Current findings on the heavy metal content in herbal drugs. Pharmeur Sci Notes 1:37–49

    Google Scholar 

  87. Cooper K, Noller B, Connell D et al (2007) Public health risks from heavy metals and metalloids present in traditional Chinese medicines. J Toxicol Environ Health A 70:1694–1699

    Article  PubMed  CAS  Google Scholar 

  88. Bhat R, Kiran K, Arun AB (2010) Determination of mineral composition and heavy metal content of some nutraceutically valued plant products. Food Anal Methods 3:181–187

    Article  Google Scholar 

  89. Ahmed MT, Loutfy N, Yousef Y (2001) Contamination of medicinal herbs with organophosphorus insecticides. Bull Environ Contam Toxicol 66:421–426

    Article  PubMed  CAS  Google Scholar 

  90. Wong TC, Lee FS, Hu GL et al (2007) A survey of heavy metal and organochlorine pesticide contaminations on commercial Lingzhi products. J Food Drug Anal 15:472–479

    CAS  Google Scholar 

  91. Sarkhail P, Yunesian M, Ahmadkhaniha R et al (2012) Levels of organophosphorus pesticides in medicinal plants commonly consumed in Iran. Daru J Pharm Sci 20:9

    Article  CAS  Google Scholar 

  92. Tong M, Gao W, Jiao W et al (2017) Uptake, translocation, metabolism, and distribution of glyphosate in nontarget tea plant (Camellia sinensis L.). J Agric Food Chem 65:7638–7646

    Article  PubMed  CAS  Google Scholar 

  93. Raman P, Patino LC, Nair MG (2004) Evaluation of metal and microbial contamination in botanical supplements. J Agric Food Chem 52:7822–7827

    Article  PubMed  CAS  Google Scholar 

  94. Abou-Arab AAK, Soliman Kawther M, Tantawy MEEI et al (1999) Quantity estimation of some contaminants in commonly used medicinal plants in the Egyptian market. Food Chem 67:357–363

    Article  CAS  Google Scholar 

  95. Bungo A, Almodovar AAB, Pereira TC (2006) Occurrence of toxigenic fungi in herbal drugs. Braz J Microbiol 37:47–51

    Article  Google Scholar 

  96. Santos L, Marin S, Sanchis V et al (2009) Screening of mycotoxin multicontamination in medicinal and aromatic herbs sampled in Spain. J Sci Food Agric 89:1802–1807

    Article  CAS  Google Scholar 

  97. Romagnoli B, Menna V, Gruppioni N et al (2007) Aflatoxins in spices, aromatic herbs, herb-teas, and medicinal plants marketed in Italy. Food Control 18:697–701

    Article  CAS  Google Scholar 

  98. Prado G, Altoé AF, Gomes TC et al (2012) Occurrence of aflatoxin B1 in natural products. Braz J Microbiol 43:1428–1436

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Gan F, Hou L, Zhou Y et al (2017) Effects of ochratoxin A on ER stress, MAPK signaling pathway and autophagy of kidney and spleen in pigs. Environ Toxicol 32:2277–2286

    Article  PubMed  CAS  Google Scholar 

  100. Gupta RC, Lasher MA, Miller Mukherjee IR, Srivastava A, Lall R (2017) Aflatoxins, ochratoxins, and citrinin. In: Gupta RC (ed) Reproductive and developmental toxicology, 2nd edn. Academic Press/Elsevier, Amsterdam, pp 945–962

    Chapter  Google Scholar 

  101. Gupta RC, Srivastava A, Lall R (2018) Ochratoxins and citrinin. In: Gupta RC (ed) Veterinary toxicology: basic and clinical principles, 3rd edn. Academic Press/Elsevier, Amsterdam, pp 1019–1027

    Chapter  Google Scholar 

  102. Ostry V, Malir F, Ruprich J (2013) Producers and important dietary sources of ochratoxin A and citrinin. Toxins 5(9):1574–1586

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Gulati K, Anand R, Ray A (2016) Nutraceuticals as adaptogens: their role in health and disease. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 193–205

    Chapter  Google Scholar 

  104. Ajayi AM, Umukoro S, Ben-Aju B et al (2017) Toxicity and protective effect of phenolic- enriched ethylacetate fraction of Ocimum gratissimum (Linn.) leaf against acute inflammation and oxidative stress in rats. Drug Dev Res 78:135–145

    Article  PubMed  CAS  Google Scholar 

  105. Burnaz NA, Kücük M, Akar Z (2017) An on-line HPLC system for detection of antioxidant compounds in some plant extracts by comparing three different methods. J Chromatogr B 1052:66–72

    Article  CAS  Google Scholar 

  106. Sobrinho AP, Minho AS, Ferreira LLC et al (2017) Characterization of anti-inflammatory effect and possible mechanism of action of Tibouchina granulosa. J Pharm Pharmacol 69:706–713

    Article  PubMed  CAS  Google Scholar 

  107. Wang K (2016) Adverse reaction prediction and pharmacovigilance of nutraceuticals: examples of computational and statistical analysis on big data. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 239–248

    Chapter  Google Scholar 

  108. Peterson JD (2016) Noninvasive in vivo optical imaging models for safety and toxicity testing. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 305–317

    Chapter  Google Scholar 

  109. Barnet RE, Bailey DC, Hatfield HE, Fitsanakis VA (2016) Caenorhabditis elegans: a model organism for nutraceutical safety and toxicity evaluation. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 341–354

    Google Scholar 

  110. Bian W-P, Pei D-S (2016) Zebrafish model for safety and toxicity testing of nutraceuticals. In Gupta RC (ed): Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 333–339

    Chapter  Google Scholar 

  111. Krishna G, Gopalakrishnan G (2016) Alternative in vitro models for safety and toxicity evaluation of nutraceuticals. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 355–385

    Chapter  Google Scholar 

  112. Kadakkuzha BM, Liu X-A, Swarnkar S, Chen Y (2016) Genomic and proteomic mechanisms and models in toxicity and safety evaluation of nutraceuticals. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 227–237

    Chapter  Google Scholar 

  113. Gonzalez-Suarez I, Martin F, Hoenig J, Peitsch MC (2016) Mechanistic network models in safety and toxicity evaluation of nutraceuticals. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 287–304

    Chapter  Google Scholar 

  114. Mindukshew I, Kudryavtsev I, Serebriakova M et al (2016) Flow cytometry and light scattering technique in evaluation of nutraceuticals. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 319–332

    Chapter  Google Scholar 

  115. Anadón A, Martínez-Laraaga MR, Ires I et al (2016) Interactions between nutraceuticals/nutrients and therapeutic drugs. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 855–874

    Chapter  Google Scholar 

  116. Sechi S, Di Cerbo A, Canello S et al (2016) Effects in dogs with behavioral disorders of a commercial nutraceutical diet on stress and neuroendocrine parameters. Vet Rec. https://doi.org/10.1136/vr.103865

  117. Mouly S, Lloret-Linares C, Sellier PO et al (2017) Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John’s Wort? Pharmacol Res 18:82–92

    Article  CAS  Google Scholar 

  118. Mooiman KD, Maas-Bakker RF, Hendrikx JJ et al (2014) The effect of complementary and alternative medicines on CYP3A4-mediated metabolism of three different substrates: 7-benzyloxy-4-trifluoromethyl-coumarin, midazolam and docetaxel. J Pharm Pharmacol 166(6):865–874

    Google Scholar 

  119. Oh HA, Lee H, Kim D et al (2017) Development of GC-MS based cytochrome P450 assay for the investigation of multi-herb interaction. Anal Biochem 519:71–83

    Article  PubMed  CAS  Google Scholar 

  120. Shao F, Zhang H, Xie L et al (2017) Pharmacokinetics of ginkgolides A, B and K after single and multiple intravenous infusions and their interactions with midazolam in healthy Chinese male subjects. Eur J Clin Pharmacol 73:537–546

    Article  PubMed  CAS  Google Scholar 

  121. Zhang L, Sparreboom A (2017) Predicting transporter-mediated drug interactions. Clin Pharmacol Ther 101(4):447–449

    Article  PubMed  CAS  Google Scholar 

  122. Gaudineau C, Beckerman R, Welbourn S et al (2004) Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem Biophys Res Commun 318(4):1072–1078

    Article  PubMed  CAS  Google Scholar 

  123. Unger M, Frank A (2004) Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Sptectrom 18:2273–2281

    Article  CAS  Google Scholar 

  124. Goey AK, Mooiman KD, Beijnen JH et al (2013) Relevance of in vitro and clinical data for predicting CYP3A4-mediated herb-drug interactions in cancer patients. Cancer Treat Rev 39:773–778

    Article  PubMed  CAS  Google Scholar 

  125. Durr D, Stieger B, Kullak-Ublick GA et al (2000) St. John’s Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 68:598–604

    Article  PubMed  CAS  Google Scholar 

  126. Dormán G, Flachner B, Hajdú I, András CD (2016) Target identification and polypharmacology of nutraceuticals. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 263–286

    Chapter  Google Scholar 

  127. Herr M, Grondin H, Sanchez S et al (2017) Polypharmacy and potentially inappropriate medications: a cross-sectional analysis among 451 nursing homes in France. Eur J Clin Pharmacol 73:601–608

    Article  PubMed  Google Scholar 

  128. Heuberger R (2012) Polypharmacy and food-drug interactions among older persons: a review. J Nutri Gerontol Geriatr 31:325–403

    Article  Google Scholar 

  129. Gochfeld M (2017) Sex differences in human and animal toxicology: toxicokinetics. Toxicol Pathol 45:172–118

    Article  PubMed  Google Scholar 

  130. Lee KW, Bode AM, Dong Z (2011) Molecular targets of phytochemicals for cancer prevention. Nat Rev Cancer 11:211–218

    Article  PubMed  CAS  Google Scholar 

  131. Posma JM, Garcia-Perez I, Heaton JC et al (2017) Integrated analytical and statistical two-dimensional spectroscopy strategy for metabolite identification: application to dietary biomarkers. Anal Chem 89:3300–3309

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Penman AD, Kaufman GE, Daniels KK (2014) MicroRNA expression as an indicator of tissue toxicity. In: Gupta RC (ed) Biomarkers in toxicology. Academic Press/Elsevier, Amsterdam, pp 1003–1018

    Chapter  Google Scholar 

  133. Srivastava A, Kumar A, Thomas JD et al (2017) Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study. Lancet Glob Health 5:e458–e466

    Article  Google Scholar 

  134. Hsu CC, Lin MH, Cheng JT et al (2017) Antihyperglycemic action of diosmin, a citrus flavonoid, is induced through endogenous-endorphin in type I-like diabetes rats. Clin Exp Pharmacol Physiol 44:549–555

    Article  PubMed  CAS  Google Scholar 

  135. Sander J, Terhardt M, Sander S et al (2017) Quantification of methylenecyclopropyl compounds and acyl conjugates by UPLC-MS/MS in the study of the biochemical effects of the ingestion of canned Ackee (Blighia sapida) and Lychee (Litchi chinensis). J Agric Food Chem 65:2603–2608

    Article  PubMed  CAS  Google Scholar 

  136. Gupta RC (2014) Biomarkers in toxicology. Academic Press/Elsevier, Amsterdam. 1128 pages

    Google Scholar 

  137. Rao N, Spiller HA, Hodges NL et al (2017) An increase in dietary supplement exposures reported to US poison control centers. J Med Toxicol 13:227–237

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Coulson JM, Caparrota TM, Thompson JP (2017) The management of ventricular dysrhythmia in aconite poisoning. Clin Toxicol 55:313–321

    Article  CAS  Google Scholar 

  139. Cope RB (2005) Toxicology brief: Allium species poisoning in dogs and cats. Vet Med:462–566

    Google Scholar 

  140. IARC (2002) Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. Aristolochia species and aristolochic acids. IARC monographs on the evaluation of carcinogenic risks to humans, vol 82. WHO, Lyon, pp 69–128

    Google Scholar 

  141. Pelkonen O, Abass K, Wiesner J (2013) Thujone and Thujone-containing herbal medicinal and botanical products: toxicological assessment. Reg Toxcicol Pharmacol 65:100–107

    Article  CAS  Google Scholar 

  142. Heise CW, Brooks DE (2017) Ayahuasca exposure: descriptive analysis of calls to US poison control centers from 2005 to 2015. J Med Toxicol 13:245–248

    Article  PubMed  CAS  Google Scholar 

  143. Ma J, Li X (2017) MicroRNAs are involved in the toxicity of microcystins. Toxin Rev 36(2):167–175

    Article  CAS  Google Scholar 

  144. McClellan NL, Manderville RA (2017) Toxic mechanisms of microcystins in mammals. Toxicol Res 6:391–405

    Article  Google Scholar 

  145. NTP-National Toxicology Program (2004) NTP Technical report on the toxicology and carcinogenesis studies of trans-cinnamaldehyde (microcapsulated) in F344/N rats and B6C3F1 mice (feed studies). February 2004, http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr514.pdf

  146. Jones AW (2017) Review of caffeine-related fatalities along with postmortem blood concentrations in 51 poisoning deaths. J Anal Toxicol 41:167–172

    Article  PubMed  CAS  Google Scholar 

  147. Zhang ZY, Lin DJ, Li WM et al (2017) Sensitive bromide-based screening of potential toxic Furanoids in Dioscorea bulbifera L. J Chromat B. Analyt Techn Biomed. Life Sci 1057:1–14

    CAS  Google Scholar 

  148. Gee P, Jackson S, Easton J (2010) Another bitter pill: a case of toxicity from DMAA party pill. J N Z Med Assoc 123:124–127

    Google Scholar 

  149. De Quadros APO, Mazzeo DEC, Marin-Morales MA et al (2017) Fruit extract of the medicinal plant Crataegus oxyacantha exerts genotoxic and mutagenic effects in cultured cells. J Toxicol Environ Health Part A 80:161–170

    Article  CAS  Google Scholar 

  150. Saito M, Ueno M, Ogino S et al (2005) High dose of Garcinia cambogia is effective in suppressing fat accumulation in developing male Zucker obese rats, but highly toxic to the testis. Food Chem Toxicol 43:411–419

    Article  PubMed  CAS  Google Scholar 

  151. Melough MM, Vance TM, Lee SG et al (2017) Furocoumarin kinetics in plasma and urine of healthy adults following consumption of grapefruit (Citrus paradisi Macf.) and grapefruit juice. J Agric Food Chem 65(14):3006–3012

    Article  CAS  PubMed  Google Scholar 

  152. Mazzanti G, Menniti-Ippolito F, Moro PA et al (2009) Hepatotoxicity from green tea: a review of the literature and two unpublished cases. Eur J Clin Pharmacol 65:331–341

    Article  PubMed  Google Scholar 

  153. Teschke R, Schulze J (2010) Risk of kava hepatotoxicity and the FDA consumer advisory. JAMA 304:2174–2175

    Article  PubMed  CAS  Google Scholar 

  154. Dale O, Ma G, Gemelli C et al (2012) Effects of mitragynine and its derivatives on human opioid receptors (delta, kappa, and mu). Planta Med Congress Abstract 78:91

    Google Scholar 

  155. Pessayre D, Mansouri A, Haouzi D et al (1999) Hepatotoxicity due to mitochondrial dysfunction. Cell Biol Toxicol 15:367–373

    Article  PubMed  CAS  Google Scholar 

  156. Liu Q, Zhao X, Lu X et al (2012) Proteomic study on usnic acid-induced hepatotoxicity in rats. J Agric Food Chem 60:7312–7317

    Article  PubMed  CAS  Google Scholar 

  157. Yokouchi Y, Imaoka M, Niino N et al (2017) Comprehensive evaluation of (+)-usnic acid-induced cardiotoxicity in rats by sequential cross-omics analysis. Toxicol Pathol 45:481–492

    Article  PubMed  CAS  Google Scholar 

  158. Sudekum M, Poppenga RH, Raju N et al (1992) Pennyroyal oil toxicosis in a dog. J Am Vet Med Assoc 200:817–818

    PubMed  CAS  Google Scholar 

  159. Nowak A, Sojka M, Klewicka E et al (2017) Ellagitannins from Rubus idaeus L exert geno- and cytotoxic effects against human colon adenocarcinoma cell line Caco-2. J Agric Food Chem 65:2947–2955

    Article  CAS  PubMed  Google Scholar 

  160. Assmann G, Cullen P, Erbey J et al (2006) Plasma sitosterol elevations are associated with increased incidence of coronary events in men: results of a nested case-control analysis of the prospective cardiovascular Münster (PROCAM) study. Nutr Metab Cardiovasc Dis 16:13–21

    Article  PubMed  CAS  Google Scholar 

  161. Macgregor FB, Abernethy VE, Dahabra S et al (1989) Hepatotoxicity of herbal remedies. Br Med J 299:1156–1157

    Article  CAS  Google Scholar 

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Acknowledgment

The authors would like to thank Ms. Robin B. Doss for her technical assistance in preparation of this chapter.

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Authors and Affiliations

  1. Toxicology Department, Breathitt Veterinary Center, Murray State University, Hopkinsville, KY, USA

    Ramesh C. Gupta

  2. Vets Plus Inc., Menomonie, WI, USA

    Ajay Srivastava & Rajiv Lall

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  1. Ramesh C. Gupta
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  2. Ajay Srivastava
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  3. Rajiv Lall
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Correspondence to Ramesh C. Gupta .

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  1. Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Bari, Italy

    Orazio Nicolotti

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Gupta, R.C., Srivastava, A., Lall, R. (2018). Toxicity Potential of Nutraceuticals. In: Nicolotti, O. (eds) Computational Toxicology. Methods in Molecular Biology, vol 1800. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7899-1_18

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  • DOI: https://doi.org/10.1007/978-1-4939-7899-1_18

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