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Effect of Acute Copper Exposure on Gastrointestinal Permeability in Healthy Volunteers

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Abstract

In vitro studies indicate that treating cells with copper results in alteration of tight junction permeability. In humans, ingestion of a single bolus of up to 10 mg Cu/L (as copper sulfate) causes nausea and vomiting in approximately 20 and 5% of the volunteers, respectively. To understand better the gastric and intestinal effects of copper, in this study we evaluated in asymptomatic volunteers (1) the effects of acute copper ingestion on gastric and intestinal permeability and (2) whether the appearance of gastrointestinal symptoms is associated with changes in mucosal permeability. Thirty-one asymptomatic subjects were assessed in a randomized, double-blind, crossover study that included two permeability tests, one after ingesting 200 ml distilled water and the other after ingesting 200 ml water containing 10 mg Cu/L (as copper sulfate). Fifteen minutes after ingestion subjects drank a second solution containing 40 g sucrose, 7.5 g lactulose, and 2 g mannitol, and urine was collected for 5 hr. Sugar concentrations were determined by gas chromatography. Symptoms during the trials were recorded in self-administered questionnaires. Ingestion of the 10 mg/L copper solution significantly increased gastric permeability to sucrose [20.8 (11.8–73.4) vs 28.4 (16.6–113.9) mg, respectively; P = 0.0064] but did not change intestinal permeability to lactulose/mannitol [0.87 (0.53–2.06) vs 1.17 (0.58–2.39)%, respectively; P = 0.18]. Gastrointestinal symptoms were reported during both the basal and the experimental conditions, but after copper ingestion they increased to 22.6% of the subjects and were significantly more intense than under basal conditions (P = 0.047). However, changes in permeability were not related to the appearance of symptoms. These results indicate that acute oral exposure to 10 mg Cu/L exerts an effect on gastric but not intestinal mucosa, reducing the gastric mucosal barrier capacity, independently of the appearance of gastrointestinal symptoms.

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REFERENCES

  1. Eife R, Weiss M, Barros V, Sigmund B, Goriup U, Komb D, Wolf W, Kittel J, Schramel P, Reiter K: Chronic poisoning by copper in tap water: I. Copper intoxications with predominantly gastrointestinal symptoms. Eur J Med Res 4:219–223, 1999

    Google Scholar 

  2. Eife R, Weiss M, Muller-Hocker M, Lang T, Barros V, Sigmund B, Thanner F, Welling P, Lange H, Wolf W, Rodeck B, Kittel J, Schramel P, Reiter K: Chronic poisoning by copper in tap water: II. Copper intoxications with predominantly systemic symptoms. Eur J Med Res 4: 224–228, 1999

    Google Scholar 

  3. Knobeloch L, Ziarnik M, Howard J, Theis B, Farmer D, Anderson H, Proctor M: Gastrointestinal upsets associated with ingestion of copper contaminated water.Environ Health Perspect 102: 958–961, 1994

    Google Scholar 

  4. Gill JS, Bhagar CI: Acute copper poisoning from drinking lime cordial prepared and left overnight in an old urn. Med J Aust 170: 510, 1999

    Google Scholar 

  5. Yelin G, Taff ML, Sadowski GE: Copper toxicity following massive ingestion of coins. Am J Forens Med Pathol 1:78–85, 1987

    Google Scholar 

  6. Olivares M, Araya M, Pizarro F, Uauy R: Nausea threshold in apparently healthy individuals who drink fluids containing graded concentrations of copper. Reg Toxicol Pharmacol (in press), 2001

  7. Niijima A, jiang ZY, Daunton NG, Fox RA: Effect of copper sulphate on the rate of the afferent discharge in the gastric branch of the vagus nerve in the rat. Neurosci Lett 80:71–74, 1987

    Google Scholar 

  8. Franco I, Doria D: Prostaglandins and nitric oxide in coppercomplex mediated protection against ethanol-induced gastric damage. Pharmacol Res 36: 395–399, 1997

    Google Scholar 

  9. Fujita T, Sakuma S, Takahashi K, Bohtani Y, Nishida H, Fujimoto Y: Inhibition of rabbit gastric glucosamine synthetase activity by Cu2+, Zn2+ and Se4+. Res Commun Mol Pathol Pharmacol 96:203–208, 1997

    Google Scholar 

  10. Stenhammar L: Diarrhoea following contamination of drinking water with copper. Eur J Med Res 4: 217–218, 1999

    Google Scholar 

  11. Ferruza S, Scarino ML, Rotilio G, Ciriolo MR, Santaroni P, Muda AO, Sambuy Y: Copper treatment alters the permeability of tight junctions in cultured human intestinal Caco-2 cells. Am J Physiol 277: G1138–G1148, 1999

    Google Scholar 

  12. Medding JB, Sutherland LR, Byles NI, Wallace JL: Sucrose. A novel permeability marker for gastrointestinal disease. Gastroenterology 104:1619–1626, 1993

    Google Scholar 

  13. Hollander D: The intestinal permeability barrier. A hypothesis as to its regulation and involvement in Crohn' disease. Scand J Gastroenterol 27:721–726, 1992

    Google Scholar 

  14. Vera JF, Gotteland M, Chavez E, Vial MT, Kakarieka E, Brunser O: Sucrose permeability in children with gastric damage and Helicobacter pylori infection. J Pediatr Gastroenterol Nutr 24: 506–511, 1997

    Google Scholar 

  15. Gotteland M, Cruchet S, Araya M, Espinoza J, Brunser O: Permeabilidad intestinal en el primer aÑo de vida. Efecto de la diarrhea. An Esp Pediatr 49: 125–128, 1998

    Google Scholar 

  16. Linder MC, Hazegh-Azam M: Copper biochemistry and molecular biology. Am J Clin Nutr 63:797S–811S, 1996

    Google Scholar 

  17. Luza SC, Speisky H: Liver copper storage and transport during development. Implications for cytotoxicity. Am J Clin Nutr 63: 812S–820S, 1996

    Google Scholar 

  18. Olivares M, Araya M, Uauy R: Copper homeostasis in infant feeding: Genetic and environmental determinants. J Pediatr Gastroenterol Nutr (in press), 2000

  19. Olivares M, Gonzalez M, Icaza G, Uauy R: Mechanism of adaptation to copper deficit and excess in humans: Basis to assess health risk. In Proceedings of the International Workshop “Risk Assessment of Copper in the Environment,” GE Lagos, R Badilla-Ohlbaum (eds). 1997, pp 291–326

  20. Fewtrell L, Kay D, Jones F, Baker A, Mowat A: Copper in drinking water, an investigation into possible health effects. Public Health 110: 175–177, 1996

    Google Scholar 

  21. Fitzgerald DJ: Safety guidelines for copper in water. Am J Clin Nutr 67(Suppl 5): 1098S–1102S, 1998

    Google Scholar 

  22. Lagos G, Reveco F: Human exposure model for copper in drinking water in the city of Santiago, Chile. In Proceedings of the International Workshop “Risk Assessment of Copper in the Environment,” GE Lagos, R Badilla-Ohlbaum (eds). 1997, pp 291–326.

  23. Olivares M, Pizarro F, Speisky H, LÖnnerdal B, Uauy R: Copper in infant nutrition: safety of WHO provisional guideline value for copper content of drinking water. J Pediatr Gastroenterol Nutr 26: 251–257, 1998

    Google Scholar 

  24. Powell JJ, Jugdaohsingh R, Thompson RPH: The regulation of mineral absorption in the gastrointestinal tract. Proc Nutr Soc 58: 147–153, 1999

    Google Scholar 

  25. Pizarro F, Olivares M, Uauy R, Contreras P, Rebelo A, Gidi V: Acute gastrointestinal effects of graded levels of copper in drinking water. Environ Health Perspect 107: 117–121, 1999

    Google Scholar 

  26. Kayashima N, Tanaka M, Iwasaki M, Hayama T: Site of emetic action of oral copper sulfate in dogs. (I) Thresholds of various portions of gastrointestinal tract to locally applied copper sulfate. Jpn J Pharmacol 28: 775–781, 1978

    Google Scholar 

  27. Lang IM: Noxious stimulation of emesis. Dig Dis Sci 44: 58S–63S, 1999 GOTTELAND ET AL 1914 Digestive Diseases and Sciences, Vol. 46, No. 9 (September 2001)

    Google Scholar 

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Gotteland, M., Araya, M., Pizarro, F. et al. Effect of Acute Copper Exposure on Gastrointestinal Permeability in Healthy Volunteers. Dig Dis Sci 46, 1909–1914 (2001). https://doi.org/10.1023/A:1010683014390

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