Abstract
Neurologic and radiologic disorders have been reported to occur in miners inhaling manganese (Mn)-laden dust and in humans receiving long-term parenteral nutrition. These abnormalities have been attributed to Mn intoxication because of elevated serum Mn concentrations. Because the liver, by way of the bile, is the major route of Mn excretion, it is possible that anything that decreases biliary excretion could increase accumulation of Mn in the brain. The purpose of this study was to determine whether biliary ligation would increase Mn accumulation in the brain of rats that were exposed to deficient or adequate amounts of dietary manganese. The first experiment had a 2 x 3 factorial design, two levels of Mn (0 or 45 μg/g diet) and three surgical treatments (control, sham, or bile-ligation). Animals were sacrificed 10 d after being fed54Mn. In experiment 2, animals that had a sham operation or bile-ligation were sacrificed at 8 time points after being injected intraportally with54Mn complexed to albumin. The biliaryligated animals had a significantly (p < 0.001) smaller percentage of the54Mn in their brains (when expressed as a percentage of whole animal54Mn) than the sham-operated animals. Mn deficiency had a similar effect. However, we did observe an increased accumulation of the radioisotope in the brain over time. Therefore, in short-term studies, biliary-ligated rats do not appear to be a good model for Mn accumulation in the brains of people with cholestatic liver disease.
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G. Defazio, L. Soleo, R. Zefferino, and P. Livrea, Manganese toxicity in serumless dis-sociated mesencephalic and striatal primary culture,Brain Research Bulletin 40, 257–262 (1996).
L. Hurley and C. Keen, Manganese, in:Trace Elements in Human and Animal Nutrition, 5th edition Academic Press, San Diego, pp. 185–224 (1987).
J. A. Donaldson and J. A. Barbeau, Manganese neurotoxicity: possible clues to the eti-ology of human brain disorders, in:Metal Ions in Neurology and Psychiatry, S. Gabay, H. Harris, and B. T. Ho, eds., Alan R. Liss, Inc., New York, pp. 259–285 (1985).
A. Barbeau, Manganese and extrapyramidal disorders,Neurotoxicity 5, 13–35 (1984).
C. C. Huang, C. S. Lu, N. S. Chu, F. Hochberg, D. Lilienfeld, W. Olanow, and D. B. Clane, Progression after chronic manganese exposure,Neurology 43, 1479–1483 (1993).
L. A. Gottschalk, T. Rebello, M. S. Buchsbaum, H. G. Tucker, and E. L. Hodges, Abnormalities in hair trace elements as indicators of aberrant behavior,Comprehensive Psychiatry 32, 229–237 (1991).
J. M. E. Fell, A. P. Reynolds, N. Meadows, K. Khan, S. G. Long, G. Quaghebeur, W. J. Taylor, and P. J. Milla, Manganese toxicity in children receiving long-term par-enteral nutrition,Lancet 347, 1218–1221 (1996).
A. P. Reynolds, E. Kiely, and N. Meadows, Manganese in long term paediatric par-enteral nutrition,Arch. Dis. Child 71, 527–528 (1994).
M. Newland, T. Ceckler, J. Kordower, and B. Weiss, Visualizing manganese in the pri-mate basal ganglia with magnetic resonance imaging,Exp. Neurol. 106, 251–258 (1989).
H. Saito and A. Ejima, Liver dysfunction and probable manganese accumulation in the brainstem and basal ganglia,J. Neurology, Neurosurgery, Psychiatry 58, 760–761 (1995).
D. Krieger, S. Krieger, O. Jansen, P. Gass, L. Thielmann, and H. Lichtnecker, Man-ganese and chronic hepatic encephalopathy,Lancet 346, 270–274 (1995).
P. G. Reeves, F. H. Nielsen, and G. C. Fahey, AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A rodent diet,J. Nutr. 123, 1939–1951 (1993).
C. D. Davis, L. Zech, and J. L. Greger, Manganese metabolism in rats: an improved methodology for assessing gut endogenous losses,Proc. Soc. Exptl. Biol. Med. 202, 103–108 (1993).
R. A. Hauser, T. A. Zesiewicz, C. Martinez, A. S. Rosemurgy, and C. W. Olanow, Blood manganese correlates with brain magnetic resonance imaging changes in patients with liver disease,Can. J. Neurol. Sci. 23, 95–98 (1996).
R. Hauser, T. Zesiewicz, A. Rosemurgy, C. Martinez, and C. Olanow, Manganese intoxication and chronic liver failure,Ann. Neurol. 36, 871–875 (1994).
R. Lambert, Surgery of the bile duct, in:Surgery of the Digestive System in the Rat, C. C. Thomas, ed., Springfield, IL, pp. 113–153 (1965).
A. A. Valois and W. S. Webster, Retention and distribution of manganese in the mouse brain following acute exposure on postnatal day 0, 7, 14, or 42: an autoradio-graphic and gamma counting study,Toxicology 57, 315–328 (1989).
D. K. Dastur, D. K. Manghani, and K. V. Raghavendran, Distribution and fate of 54Mn in the monkey: studies of different parts of the central nervous system and other organs,J. Clin. Invest. 50, 9–20 (1971).
C. D. Davis, T. L. Wolf, and J. L. Greger, Varying levels of manganese and iron affect absorption and gut endogenous losses of manganese by rats,J. Nutr. 122, 1300–1308 (1992).
D. M. Greenburg, H. D. Copp, and E. M. Cuthbertson, Studies in mineral metabo-lism with the aid of artificial radioactive isotopes. VII. The distribution and excre-tion particularly by way of the bile, of iron, cobalt and manganese,J. Biol. Chem. 147, 749–756 (1943).
E. A. Malecki, G. W. Radzanowski, T. J. Radzanowski, D. D. Gallaher, and J. L. Greger, Biliary manganese excretion in conscious rats is affected by acute and chronic manganese intake but not by dietary fat,J. Nutr. 126, 489–498 (1996).
W. T. Burnett, R. R. Bigelow, A. W. Kimball, and G. W. Sheppard, Radiomanganese studies on the mouse, rat and pancreatic fistula dog,Am. J. Physiol. 168, 620–625 (1952).
W. J. Miller, M. W. Neathery, R. P. Gentry, D. M. Blackmon, and J. W. Lassiter, Fecal excretion, tissue accumulation and turnover of54manganese after intravenous dosing in holstein calves fed a practical-type diet,J. Anim. Sci. 37, 1284–1290 (1973).
A. B. R. Thomson, D. Olstunbosum, and L. S. Valberg, Interrelationship of intestinal transport system of manganese and iron,J. Lab. Clin. Med. 78, 643–655 (1971).
J. W.Finley, J. S.Caton, Z.Zhou, and K. L.Davison, A surgical model for determi-nation of true absorption and biliary excretion of manganese in conscious swine fed commercial diets,J. Nutr., (in press).
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The U.S. Department of Agriculture, Agriculture Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer and all agency services are available without discrimination.
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Davis, C.D., Schafer, D.M. & Finley, J.W. Effect of biliary ligation on manganese accumulation in rat brain. Biol Trace Elem Res 64, 61–74 (1998). https://doi.org/10.1007/BF02783325
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DOI: https://doi.org/10.1007/BF02783325