The gastrointestinal tract: safety pharmacology aspects relating to ageing, diet and natural/herbal remedies
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Copenhagen University Library, and The Parker Institute, Frederiksberg Hospital, Denmark
Department of Animal and Veterinary Basic Sciences, Faculty of Life Science, Copenhagen University, Frederiksberg, Denmark
Corresponding author
Adrian P. Harrison   

Department of Animal and Veterinary Basic Sciences, Faculty of Life Science, University of Copenhagen, Grønnegaardsvej 7, 1870 Frederiksberg C, Denmark.
J Pre Clin Clin Res. 2009;3(2):76-83
The gastrointestinal tract (GIT) has always been and remains a major source of interest in terms of both its function, and its malfunction. Our current knowledge of age-related changes in this system, as well as drug-food interactions, however, remains relatively limited. Paradoxically, the GIT is not one of the core battery of tests that pharmaceutical companies are obliged to investigate as part of drug development. This review aims to cover the basics of GIT function before highlighting aspects of relevance for safety pharmacology in terms of age, cancerogenesis, and both drug and diet-related GIT damage and dysfunction. New and novel aspects of drug delivery and drug-dietary supplement interactions are discussed and much needed areas of focus in terms of drug GIT testing are identified.
Long MS, Cheshire E: Crash Course: Gastrointestinal System (2nd edn)., Horton-Szar, Mosby (USA) 2002.
Salles N: Basic mechanisms of the aging gastrointestinal tract. Dig Dis 2007, 25, 112-117.
Nakamura K, Ogoshi K, Makuuchi H: Infl uence of aging, gastric mucosal atrophy and dietary habits on gastric secretion. Hepato Gastroenterol 2006, 53, 624-628.
Lee HM, Greeley GH, Englander EW: Age-associated changes in gene expression patterns in the duodenum and colon of rats. Mech Ageing Dev 2001, 122, 355-371.
Owyang C: Recent advances and future research directions in neurogastroenterology and endocrinology recommendations of the National Commission on Digestive Diseases. Neurogastroenterol Motil 2008, 20, 1189-1203.
Jadcherla SR, Duong HQ, Hofmann C, Hoff mann R, Shaker R: Characteristics of upper oesophageal sphincter and oesophageal body during maturation in healthy human neonates compared with adults. Neurogastroenterol Motil 2005, 17, 663-670.
Phillips RJ, Powley TL: As the gut ages: time tables for aging of innervation vary by organ in the Fisher 344 rat. J Comp Neurol 2001, 434, 358-377.
El-Salhy M, Sandstrom O, Holmlund F: Age-induced changes in the enteric nervous system in the mouse. Mech Aging Dev 1999, 107, 93- 103.
Nakae Y, Onouchi H, Kagaya M, Kondo T: Eff ects of aging and gastric lipolysis on gastric emptying of lipid in liquid meal. J Gastroenterol 1999, 34, 445-449.
Phillips RJ, Powley TL: Innervation of the gastrointestinal tract: Patterns of aging. Auton Neurosci 2008, 136, 1-19.
Madsen JL, Graff J: Eff ects of aging on gastrointestinal motor function. Age Ageing 2004, 33, 154-159.
Roberts D, Gelperin D, Wiley JW: Evidence for age-associated reduction in acetylcholine release and smooth muscle response in the rat colon. Am J Physiol 1994, 267, G515-G522.
Woudstra T, Thomson ABR: Nutrient absorption and intestinal adaptation with aging. Best Pract Res Clin Gastroenterol 2002, 16, 1-15.
Shames DS, Minna JD, Gazdar AF: DNA methylation in health, disease, and cancer. Curr Mol Med 2007, 7, 85-102.
Suzuki K, Suzuki I, Leodolter A, Alonso S, Horiuchi S, Yamashita K, Perucho M: Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage. Cancer Cell 2006, 9,199- 207.
Kim SK, Jang HR, Kim JH, Kim M, Noh SM, Song KS, Kang GH, Kim HJ, Kim SY, Yoo HS, Kim YS: CpG methylation in exon 1 of transcription factor 4 increases with age in normal gastric mucosa and is associated with gene silencing in intestinal-type gastric cancer. Carcinogenesis 2008, 29(8), 1623-1631.
Correa P: A human model of gastric carcinogenesis. Cancer Res 1988; 48(13), 3554-3560.
Kang KP, Lee HS, Kim N, Kang HM, Park YS, Lee DH, Choe G, Kim JS, Jung HC, Song IS: Role of intestinal metaplasia subtyping in the risk of gastric cancer in Korea. J Gastroenterol Hepatol 2008; doi: 10.1111/j.1440-1746.2008.05546.x.
Xiao R, Hennings LJ, Badger TM, Simmen FA: Fetal programming of colon cancer in adult rats: correlations with altered neonatal growth trajectory, circulating IGF-I and IGF binding proteins, and testosterone. J Endocrin 2007, 195, 79-87.
Kearney BP, Sayre JR, Flaherty JF, Chen SS, Kaul S, Cheng AK: Drug-drug interactions between Tenofovir Disoproxil Fumarate and Didanosine. J Clin Pharmacol 2005, 45, 1360-1370.
Parfi tt JR, Driman DK: Pathological eff ects of drugs on the gastrointestinal tract: a review. Human Pathol 2007, 38, 527-526.
Sherman A, Bini EJ: Pill-induced gastric injury. Am J Gastroenterol 1999, 94, 511-513.
Abraham SC, Cruz-Correa M, Lee LA, Yardley JH, Wu TT: Alendronateassociated esophageal injury: pathologic and endoscopic features. Mod Pathol 1999, 12, 1152-1157.
Boyce HW Jr: Drug-induced esophageal damage: diseases of medical progress. Gastrointest Endosc 1998, 47, 547-550.
Brunton LL, Lazo JS, Parker KL, Goodman LS, Gilman A: Goodman and Gilman’s The pharmalogical basis of therapeutics (11th edn), McGraw-Hill, New York 2006.
Akamine D, Filho MK, Pere s CM: Drug-nutrient interactions in elderly people. Curr Opin Clin Nutr Met Care 2007, 10, 304-310.
Gauthier I, Malone M: Drug-food interactions in hospitalised patients. Drug Safety 1998; 18(6), 383-393.
Lis-Balchin M: Current Topics: Serious adverse eff ects between herbal remedies and conventional drugs taken simultaneously. J Royal Soc Prom Health 2002, 122, 210.
Milbury PE, Cao G, Prior RL, Blumberg J: Bioavailability of elderberry anthocyanins. Mech Ageing Dev 2002, 123, 997-1006.
Thole JM, Burns Kraft TF, Sueiro LA, Kang YH, Gills JJ, Cuendet M, Pezzuto JM, Seigler DS, Lila MA: A comparative evaluation of the anticancer properties of European and American elderberry fruits. J Med Food 2006, 9, 498-504.
Gee JM, DuPont MS, Rhodes MJC, Johnson IT: Quercetin glucosides interact with the intestinal glucose transport pathway. Free Radic Biol Med 1998, 25, 19-25.
Paolini M, Pozzetti L, Sapone A, Cantelli-Forti G: Eff ect of liquorice and glycyrrhizin on murine liver CYP-dependent monooxygenases. Life Sci 1998, 62 571-582.
Paolini M, Narillari J, Broccoli M, Pozzetti L, Perocco P, Cantelli- Forti G: Eff ect of liquorice and glycyrrhizin on rat liver carcinogen metabolizing enzymes. Cancer Lett 1999, 145, 35-42.
Gorski J, Huang S, Pinto A, Hamman MA, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD: The eff ect of Echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin Pharmacol Ther 2004, 5, 89-100.
Barnes J, Andersen LA, Phillipson JD: Herbal medicines (2nd edn), Pharmaceutical Press (UK) 2002.
Basch EM, Ulbricht CE: Natural Standard. Herb and supplement handbook – the clinical bottom line. Mosby Inc (USA).2005.
Kane GC, Lipsky JJ: Drug-grapefruit juice interactions. Mayo Clin Proc 2000, 75, 933-942.
Dollery C: Medicine and the pharmacological revolution. J Royal Coll Phys 1994, 28, 59-69.
Kang-Yum E, Kurt TL, Smolinske S: Toxicity and drug interactions of herbs and dietary supplements. Clin Toxicol 2006, 44, 603.
Aggarwal A, Ades PA: Interactions of herbal remedies with prescription cardiovascular medications. Coronary Artery Disease 2001, 12, 581- 584.
Piscitelli S, Burstein A, Weldon N, Gallicano KD, Falloon J: The eff ect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002, 34, 234-238.
Sharma SS, Kochupillai V, Gupta SK, Seth SD, Gupta YK: Antiemetic activity of ginger (Zingiber offi cinale) against cisplatin-induced emesis in dogs. J Ethnopharmacol 1997, 57, 93-96.
Yamahara J, Huang QR, Li YH, Xu L, Fujimura H: Gastrointestinal motility enhancing eff ect of ginger and its active constituents. Chem Pharm Bull 1990; 38, 430-431.
Delgoda R, Westlake ACG: Herbal interactions involving cytochrome P450 enzymes: A mini review. Toxicol Rev 2004, 23, 239-249.
Rossi M, Negri E, Talamini R, Bosetti C, Parpinel M, Gnagnarella P, Franceschi S, Dal Maso L, Montella M, Giacosa A, La Vecchia C: Flavonoids and colorectal cancer in Italy. Cancer Epidemiol Biomark Prev 2006, 15, 1555-1558.
Schaefer HG, Heinig R, Ahr G, Adelmann H, Tetzloff W, Kuhlmann J: Pharmacokinetic-pharmacodynamic modelling as a tool to evaluate the clinical relevance of a drug-food interaction for a nisoldipine controlledrelease dosage form. Eur J Clin Pharmacol 1997, 51, 473-480.
Rapaport MH: Dietary restrictions and drug interactions with monoamine oxidase inhibitors: The state of the art. J Clin Psychiatry 2007, 68, 42-46.
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