Abstract
Long-Evans Cinnamon (LEC) rats are characterized by the sudden onset of hepatitis around 4 months after birth and the gross accumulation of hepatic copper (Cu) accompanied by metallothionein (MT). The biliary excretion of manganese (Mn) and cadmium (Cd) injected intravenously was studied in 3-month-old LEC rats without signs of hepatitis. Injected Mn was excreted into the bile in LEC and Fischer rats used for comparison. However, increased biliary excretion of Cd was found not in the LEC rat but in the Fischer rat. Excretion of horseradish peroxidase (HRP) injected along with the metal mixture was significantly lower in the LEC group than in the Fischer group. Our results suggest that Mn excretion is not related to the existence of a gross amount of Cu-MT. Reduced excretion of Cd may be partly due to binding to Cu-MT in the liver. Decreased excretion of HRP implies the existence of an inherent defect in the bile excretion route for endo-and exogenous substances.
References
Bartsch SL, Klein D, Summer KH (1990) The Cd-chelex assay: a new sensitive method to determine metallothionein containing zinc and cadmium. Arch Toxicol 64: 177–180
Chance B, Maehly AC (1955) Assay of catalases and peroxidases, In: Colowick SD, Kaplan ND (eds) Methods in enzymology, vol. II. Academic Press, New York, pp 769–775
Havrdova J, Cikrt M, Tichy M (1974) Binding of cadmium and mercury in the rat bile: studies using gel filtration. Acta Pharmacol Toxicol 34: 246–253
Klaassen CD (1974a) Biliary excretion of arsenic in rats, rabbits and dogs. Toxicol Appl Pharmacol 29: 447–457
Klaassen CD (1974b) Biliary excretion of manganese in rats, rabbits and dogs. Toxicol Appl Pharmacol 29: 458–468
Klaassen CD (1978) Effect of metallothionein on hepatic disposition of metals. Am J Physiol 234: E47-E53
Klaassen CD, Kotsonis FN (1977) Biliary excretion of cadmium in the rat, rabbit and dog. Toxicol Appl Pharmacol 41: 101–112
Klaassen CD, Shoeman DW (1974) Biliary excretion of lead in rats, rabbits and dogs. Toxicol Appl Pharmacol 29: 434–446
Li Y, Togashi Y, Sato S, Emoto T, Kang J-H, Takeichi N, Kobayashi H, Kojima Y, Une Y, Uchino J (1991) Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis: a model of Wilson's disease. J Clin Invest 87: 1858–1861
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193: 265–275
Renston RH, Maloney DG, Jones AL, Hradek GT, Wong KY, Goldfine ID (1980) Bile secretory apparatus: evidence for a vesicular transport mechanism for proteins in the rat, using horseradish peroxidase and [125I]insulin. Gastroenterology 78: 1373–1388
Sasaki M, Yoshida M, Kagami K, Takeichi N, Kobayashi H, Dempo K, Mori M (1985) Spontaneous hepatitis in an inbred strain of Long-Evans rats. Rat News Lett 14: 4–6
Shaikh ZA, Lucis OJ (1971) Isolation of cadmium-binding proteins. Experientia 27: 1024–1025
Sugawara N, Sugawara C, Katakura M, Takahashi H, Mori M (1991a) Harmful effect of administration of copper on LEC rats. Res Commun Chem Pathol Pharmacol 73: 289–297
Sugawara N, Sugawara C, Katakura M, Takahashi H, Mori M (1991b) Copper metabolism in the LEC rat: involvement of induction of metallothionein and disposition of zinc and iron. Experientia 47: 1060–1063
Sugawara N, Sugawara C, Sato M, Takahashi H, Mori M (1992) Accumulation of copper and copper-metallothionein in the liver of LEC rats with spontaneous hepatitis and hepatoma. Igakuno-Ayumi 160: 479–480 (in Japanese)
Sugawara N, Li D, Sugawara C, Miyake H (1993) Decrease in biliary excretion of copper in Long-Evans Cinnamon (LEC) rats causing spontaneous hepatitis due to a gross accumulation of hepatic copper. Res Commun Chem Pathol Pharmacol 81: 45–52
Sugawara N, Li D, Katakura M, Sugawara C (1994) Biliary excretion of copper in Fischer rats treated with copper salt and in Long-Evans Cinnamon (LEC) rats with an inherently abnormal copper metabolism. Biol Trace Element Res (in press)
Vostal JJ, Cherian MG (1974) Biliary excretion of cadmium in the rat. Toxicol Appl Pharmacol 29: 141–142
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Sugawara, N., Li, D. & Sugawara, C. Biliary excretion of exogenous cadmium and manganese in Long-Evans Cinnamon (LEC) rats characterized by an inherently gross amount of copper-metallothionein in the liver. Arch Toxicol 68, 520–523 (1994). https://doi.org/10.1007/s002040050106
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DOI: https://doi.org/10.1007/s002040050106