medigraphic.com
Órgano Oficial de la Asociación Mexicana de Hepatología

2002, Number 1

<< Back Next >>

Ann Hepatol 2002; 1 (1)

Zinc sulfate inhibits the enterohepatic cycling of unconjugated bilirubin in subjects with Gilbert’s syndrome

Méndez-Sánchez N, Martínez M, González V, Roldán-Valadez E, Flores MA, Uribe M

Language: English
References: 30
Page: 40-43
PDF size: 141.54 Kb.


Text Extraction

We have previously observed that UCB binds to ZnSO4 in vitro, and suppresed the biliary bilirubin secretion in the hamster. The aim of this study was designed to investigate whether Zn salts might inhibit the enterohepatic cycling of UCB in subjects with Gilbert´s syndrome. Fifteen patients with Gilbert´s syndrome and 5 normal healthy volunteers were included in this study according to the following criteria: fasting hyperbilirubinemia, no hemolysis, and free of any medication. Patients were randomly assigned to receive acute o chronic treatment. Subjects treated in acute form and normal healthy volunteers were treated with 40 mg of ZnSO4 in a single dose, where as patients treated in chronic form received 100 mg ZnSO4 in a single dose daily for 7 days. The serum UCB levels (mg/dL) decreased from 2.64 ± 1.04 to 2.02 ± 0.87 (p ‹ 0.001) and 1.8 ± 0.36 to 1.48 ± 0.32 (p ‹ 0.005) in subjects treated in acute an chronic form respectively, but not in the control group. Whereas, the serum Zn levels (mg/dL) increased from 96.3 ± 16.8 to 118.8 ± 19. 5, (p ‹ 0.01) and from 117.6 ± 8.5 to 130.7 ± 6.6 (p ‹ 0.03) in subjects treated in acute an chronic form and also in subjects in the control group (98.0 ± 7.3 to 128.0 ± 21.9) p ‹ 0.03. This study showed that acute and chronic oral administration of ZnSO4 decreased serum UCB levels significantly in subjects with Gilbert´s syndrome. Most likely by the inhibition of the “normal” enterohepatic cycling of UCB.


REFERENCES

  1. Berk PD, Martin JF, Blaschke TF, Scharschmidt BF, Plotz PH. Unconjugated hyperbilirubinemia: physiologic evaluation and experimental approaches to therapy. Ann Intern Med 1975; 82: 552-570.

  2. Powell LW, Hemingway E, Billing BH, Sherlock S. Idiopathic unconjugated hyperbilirubinemia (Gilbert’s syndrome): a study of 42 families. N Engl J Med 1967; 277: 1108-1112.

  3. Foulk WT, Butt HR, Owen CA, Jr., Whitcomb FF, Mason HL. Constitutional hepatic dysfunction (Gilbert’s disease): its natural history and related syndromes. Medicine (Baltimore) 1959; 38: 25-46.

  4. Bosma PJ, Roy Chowdhury J, Bakker CTM, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med 1995; 333: 1171-1175.

  5. Monaghan G, Ryan M, Seddon R, Hume R, Burchell B. Genetic variation in bilirubin UDP-glucuronosyltransferase gene promoter and Gilbert’s syndrome. Lancet 1996; 347: 578-581.

  6. Clarke DJ, Moghrabi N, Monaghan G, Cassidy A, Boxer M, Hume R, et al. Genetic defects of the UDP-glucuronosyltransferase-1 (UGT1) gene that cause familial non-hemolytic unconjugated hyperbilirubinemias. Clin Chim Acta 1997; 266: 63-74.

  7. Bancroft JD, Kreamer B, Gourley GR. Gilbert’s syndrome accelerates development of neonatal jaundice. J Pediatr 1998; 132: 656-660.

  8. Sampietro M, Lupica L, Perrero L, Romano R, Molteni V, Fiorelli G. TATA-box mutant in the promoter of the uridine diphosphate glucuronosyltransferase gene in Italian patients with Gilbert’s syndrome. Ital J Gastroenterol Hepatol 1998; 30: 194-198.

  9. Black M, Billing BH. Hepatic bilirubin UDP-glucuronyl transferase activity in liver disease and in Gilbert’s syndrome. N Engl J Med 1969; 280: 1266-1271.

  10. Felsher BF, Craig JR, Carpio N. Hepatic bilirubin glucuronidation in Gilbert’s syndrome. J Lab Clin Med 1973; 81: 829-837.

  11. Hauser SC, Gollan J. Bilirubin metabolism and hyperbilirubinemic disorders. In Millward-Sadler GH, Wright R, Arthur MJP. Wright’s liver and biliary disease. 3rd Ed. London, W.B. Saunders Company, 1992; 317-70.

  12. Fevery J, Blanckaert N, Heirwegh KPM, Preaux AM, Berhelot P. Unconjugated bilirubin and an increased proportion of bilirubin monoconjugates in the bile patients with Gilbert‘s syndrome and Crigler Najjar disease. J Clin Invest 1977; 60: 970-979.

  13. Spivak W, Carey MC. Reverse-phase h.p.l.c. separation, quantification and preparation of bilirubin and its conjugates from native bile. Biochem J 1985; 225: 287-805.

  14. Brink AM, Méndez-Sánchez N, Carey MC. 1996. Bilirubin cycles enterohepatically after ileal resection in the rat. Gastroenterology. 1996; 110: 1945-1957.

  15. Brink MA, Slors JF, Keulemans YC, Mok KS, De Waart DR, Carey MC, et al. Enterohepatic cycling of bilirubin: a putative mechanism for pigment gallstone formation in ileal Crohn’s disease. Gastroenterology 1999; 116: 1420-7.

  16. Dawes LG, Stryler S, Rege R, Nahrwold D. Gallbladder bile composition in Crohn’s disease. Surgical Forum. 1991; 42: 188-189.

  17. Méndez-Sánchez N, Roldán-Valadez E, Flores MA, Cárdenas-Vázquez R, Uribe M. Zinc Salts Precipitate Unconjugated Bilirubin In Vitro and Inhibit Enterohepatic Cycling of Bilirubin in Hamsters. Eur J Clin Invest 2001; 31: 773-80.

  18. Blackaert N. Analysis of bilirubin and bilirubin mono and diconjugates. Determination of their relative amounts in biological samples. Biochem J 1980; 185: 115-128.

  19. Snedecor GW, Cochran WG. Statistical methods. Ames Iowa: The Iowa State University Press 1972.

  20. Moore EW. The role of calcium in the pathogenesis of gallstones: Ca++ electrode studies of model bile salt solutions and other biological systems. Hepatology 1984; 4: 228S-43S.

  21. Sutor DJ, Wilkie LI. Calcium in bile and calcium salts in gallstones. Clin Chem Acta 1977; 79: 119-127.

  22. Dawes LG, Nahrwold DL, Rege RV. Increased total and free ionized calcium in a canine model of pigment gallstones. Surgery 1988; 104: 86-90.

  23. Oyama JH. Hyperbilirubinemia in healthy males or acutely restricted dietary intake receiving parenteral nutrition. Abstract. Am J Clin Nutr 1972; 25: 459.

  24. Gollan JL, Bateman C, Billing BH. Effect of dietary composition on the unconjugated hyperbilirubinemia of Gilbert´s syndrome. Gut 1976; 17: 335-340.

  25. Ostrow JL, Celic L. Bilirubin chemistry, ionization and solubilization by bile salts. Hepatology 1984; 4: 38S-45S.

  26. Stauffer JQ, Steward RJ, Bertrand G. Acquired hyperoxaluria: relationship to dietary calcium content and severity of steatorrhea. Gastroenterology 1974; 66: 783). 122.

  27. Earnest DL. Enteric hyperoxaluria. Adv Intern Med 1979; 24: 407-27.

  28. Caspary WF, Tönissen J, Lankisch PG. “Enteral” Hyperoxaluria. Effect of cholaestryramine, calcium, neomycin, and bile acids on intestinal oxalate absorption in man. Acta Hepato-Gastroenterol 1977; 24: 193-200.

  29. Van der Veere CN, Jansen PL, Sinaasappel M, Van der Meer R, Van der Sijs H, Rammeloo JA, Goyens P, Van Nieuwkerk CM, Oude Elferink RP. Oral calcium phosphate: a new therapy for Crigler-Najjar disease? Gastroenterology 1997; 112: 455-62.

  30. Dashti HM, Mathew TC, Jadaon MM, Ashkanani E. Zinc and liver cirrhosis: biochemical and histopathologic assessment. Nutrition 1997; 13: 206-12.




2020     |     www.medigraphic.com