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October 1966, Vol 112, No. 4 >
Article | October 1966

Bilirubin in the Liver and Kidney in Jaundiced Rats FREE

GERARD B. ODELL, MD; JURGEN C. NATZSCHKA, MD; BRUCE STOREY, MB
[+] Author Affiliations

Received for publication April 6, 1966.

Submitted by the authors for the Daniel C. Darrow Festschrift issue of the JOURNAL.

Reprint requests to 601 N Broadway, Baltimore 21205 (Dr. Odell).


Am J Dis Child. 1966;112(4):351-358. doi:10.1001/archpedi.1966.02090130125012.
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References
Comments

IN A PREVIOUS balance of bilirubin from this laboratory, retention of bilirubin occurred in extravascular tissue spaces.1 When 8 mg of bilirubin/100 gm of mature rat was infused during a 60-minute interval, the animals excreted 40%. Of the retained bilirubin, 25% was accounted for by direct analysis in the plasma and 7% in adipose tissue. The remaining 68% of the retained bilirubin was presumed to be in extravascular tissue spaces which were non-adipose. This "residual" bilirubin was derived by arithmetic difference from the balance rather than from direct analysis. A more direct measurement of the residual bilirubin and particularly its intracellular distribution was desired.

One obvious location for significant quantities of infused bilirubin is in the liver. A number of investigations have demonstrated the rapidity with which the liver can remove bilirubin from the circulating plasma and excrete it in bile as its conjugated derivatives,2-4 Schmid and co-workers

REFERENCES

1 +
Natzschka, J.C., and Odell, G.B.:  The Influence of Albumin on the Distribution and Excretion of Bilirubin in Jaundiced Rats , Pediatrics 37:51, 1966;.
2 +
Weinbren, K., and Billing, B.H.:  Hepatic Clearance of Bilirubin as an Index of Cellular Function in the Regenerating Rat Liver , Brit J Exp Path 37: 199, 1956;.
3 +
Arias, I.M.; Johnson, L.; and Wolfson, S.:  Biliary Excretion of Injected Conjugated and Unconjugated Bilirubin by Normal and Gunn Rats , Amer J Physiol 200:1091, 1961;.
4 +
Ostrow, J.D.; Jandl, J.H.; and Schmid, R.:  The Formation of Bilirubin From Hemoglobin in Vivo , J Clin Invest 41:1628, 1962;.
5 +
Schmid, R., and Hammaker, L.:  Metabolism and Disposition of C14-Bilirubin in Congenital Non-Hemolytic Jaundice , J Clin Invest 42:1720, 1963;.
6 +
Hargreaves, T., and Lathe, G.H.:  Inhibitory Aspects of Bile Secretion , Nature 200:1172, 1963;.
7 +
Acocella, G., and Billing, B.H.:  "Effect of Drugs on the Hepatic Transport of Bilirubin,"  in McIntyre, N., and Sherlock, S., (eds.): Therapeutic Agents and the Liver , Philadelphia: F. A. Davis Company, 1965;, p 1.
8 +
Brown, W.R.; Grodsky, G.M.; and Carbone, J.V.:  Intracellular Distribution of Tritiated Bilirubin During Hepatic Uptake and Excretion , Amer J Physiol 207:1237, 1964;.
9 +
Bernstein, L., et al:  Hepatic Intracellular Distribution of Tritiated Unconjugated Bilirubin and Conjugated Bilirubin in Normal and Gunn Rats , Clin Res 12:446, 1964;.
10 +
Pickens, M.; Anderson, W.E.; and Smith, A.H.:  The Composition of Gains Made by Rats on Diets Promoting Different Rates of Gain , J Nutr 20:351, 1940;.
11 +
Huang, K.C., and Bondurant, J.H.:  Simultaneous Estimation of Plasma Volume, Red Cell Volume, and Thiocyanate Space in Unanesthetized Normal and Splenectomized Rats , Amer J Physiol 185:441, 1956;.
12 +
deDuve, C., et al:  Tissue Fractionation Studies. 6. Intracellular Distribution Patterns of Enzymes in Rat-Liver Tissue , Biochem J 60:604, 1955;.
13 +
Appelmans, F.; Wattiaux, R.; and deDuve, C.:  Tissue Fractionation Studies: 5. The Association of Acid Phosphatase With a Special Class of Cytoplasmic Granules in Rat Liver , Biochem J 59:438, 1955;.
14 +
Malloy, H.T., and Evelyn, K.A.:  The Determination of Bilirubin With the Photoelectric Colorimeter , J Biol Chem 119:481, 1955;.
15 +
Odell, G.B.:  The Distribution of Bilirubin Between Albumin and Mitochondria , J Pediat 68:164, 1966;.
16 +
Weber, A.P., and Schalm, L.:  Quantitative Separation and Determination of Bilirubin and Conjugated Bilirubin in Human Serum , Clin Chem Acta 7:805, 1962;.
17 +
Stetten, M.R.:  Metabolism of Inorganic Pyrophosphate: 1. Microsomal Inorganic Pyrophosphate Phosphotransferase of Rat Liver , J Biol Chem 239: 3576, 1964;.
18 +
Smith, L.:  "Spectrophotometric Assay of Cytochrome C Oxidase,"  in Glick, D. (ed.): Methods of Biochemical Analysis , New York: Interscience Publishers, Inc., 1958;, vol II, p 427.
19 +
Barber-Riley, G.:  Measurement of Capacity of Biliary Tree in Rats , Amer J Physiol 205:1122, 1963;.
20 +
Matthews, C.M.E.; Bruce-Robertson, A.; and Humphrey, J.H.:  "Measurement of Extravascular Albumin in Normal Rabbits and Rats,"  in Plasma Proteins and Gastrointestinal Tract in Health and Disease , Baltimore: Williams & Wilkins Co., 1963;, p 36.
21 +
Dewey, W.C.:  Vascular-Extravascular Exchanges of I131-Plasma Proteins in the Rat , Amer J Physiol 197:423, 1959;.
22 +
Grodsky, G.M., et al:  Distribution of Bilirubin-H3 in the Fetal and Maternal Rat , Amer J Physiol 204:837, 1963;.
23 +
Dittmer, D.S., and Grebe, R.M. (eds.): Handbook of Circulation , Philadelphia: W. B. Saunders, Co., 1959;, pp 127, 129.
24 +
Martin, N.H.:  Preparation and Properties of Serum and Plasma Proteins: XXI. Interactions With Bilirubin , J Amer Chem Soc 71:1230, 1949;.
25 +
Klatskin, G., and Bungards, L.:  Bilirubin Protein Linkages in Serum and Their Relationship to the van den Bergh Reaction , J Clin Invest 35:537, 1956;.
26 +
Odell, G.B.:  Studies in Kernicterus. 1. The Protein Binding of Bilirubin , J Clin Invest 38:823, 1959;.
27 +
Lester, R., and Schmid, R.:  Bilirubin Metabolism , New Eng J Med 270:779, 1964;.
28 +
Stevenson, J.H., and Dutton, G.J.:  Glucuronide Synthesis in Kidney and Gastrointestinal Tract , Biochem J 82:330, 1962;.
29 +
Williamson, J.; Robinson, R.R.; and Owen, E.E.:  Mechanism of Bilirubin Excretion by Avian Kidney , Amer J Physiol 205:267, 1963;.
30 +
Schenker, S., and McCandless, D.W.:  Renal Disposition of Conjugated Bilirubin in Aglomerular Fish , Nature 202:1344, 1964;.
31 +
Fulop, M.; Sandson, J.; and Brazeau, P.:  Dialyzability, Protein Binding and Renal Excretion of Plasma Conjugated Bilirubin , J Clin Invest 44: 666, 1965;.
32 +
Odell, G.B.:  The Influence of pH on the Distribution of Bilirubin Between Albumin and Mitochondria , Proc Soc Exp Biol Med 120:352, 1965;.
33 +
Gartner, L.M., and Arias, J.M.:  Developmental Pattern of Glucuronide Formation in Rat and Guinea Pig Liver , Amer J Physiol 205:663, 1963;.
34 +
Dutton, G.J.; Langelaan, D.E.; and Ross, P.E.:  High Glucuronide Synthesis in Newborn Liver: Choice of Species and Substrate , Biochem J 93:4P, 1964;.
35 +
Boerth, R.D.; Blast, A.H.; and Spratt, J.T.:  Limitations in the Determination of in Vitro Bilirubin Glucuronide Formation , J Lab Clin Med 65: 475, 1965;.
36 +
Brown, A.K., and Zuelzer, W.W.:  Studies on Neonatal Development of Glucuronide Conjugating Systems , J Clin Invest 37:332, 1958;.

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References

1 +
Natzschka, J.C., and Odell, G.B.:  The Influence of Albumin on the Distribution and Excretion of Bilirubin in Jaundiced Rats , Pediatrics 37:51, 1966;.
2 +
Weinbren, K., and Billing, B.H.:  Hepatic Clearance of Bilirubin as an Index of Cellular Function in the Regenerating Rat Liver , Brit J Exp Path 37: 199, 1956;.
3 +
Arias, I.M.; Johnson, L.; and Wolfson, S.:  Biliary Excretion of Injected Conjugated and Unconjugated Bilirubin by Normal and Gunn Rats , Amer J Physiol 200:1091, 1961;.
4 +
Ostrow, J.D.; Jandl, J.H.; and Schmid, R.:  The Formation of Bilirubin From Hemoglobin in Vivo , J Clin Invest 41:1628, 1962;.
5 +
Schmid, R., and Hammaker, L.:  Metabolism and Disposition of C14-Bilirubin in Congenital Non-Hemolytic Jaundice , J Clin Invest 42:1720, 1963;.
6 +
Hargreaves, T., and Lathe, G.H.:  Inhibitory Aspects of Bile Secretion , Nature 200:1172, 1963;.
7 +
Acocella, G., and Billing, B.H.:  "Effect of Drugs on the Hepatic Transport of Bilirubin,"  in McIntyre, N., and Sherlock, S., (eds.): Therapeutic Agents and the Liver , Philadelphia: F. A. Davis Company, 1965;, p 1.
8 +
Brown, W.R.; Grodsky, G.M.; and Carbone, J.V.:  Intracellular Distribution of Tritiated Bilirubin During Hepatic Uptake and Excretion , Amer J Physiol 207:1237, 1964;.
9 +
Bernstein, L., et al:  Hepatic Intracellular Distribution of Tritiated Unconjugated Bilirubin and Conjugated Bilirubin in Normal and Gunn Rats , Clin Res 12:446, 1964;.
10 +
Pickens, M.; Anderson, W.E.; and Smith, A.H.:  The Composition of Gains Made by Rats on Diets Promoting Different Rates of Gain , J Nutr 20:351, 1940;.
11 +
Huang, K.C., and Bondurant, J.H.:  Simultaneous Estimation of Plasma Volume, Red Cell Volume, and Thiocyanate Space in Unanesthetized Normal and Splenectomized Rats , Amer J Physiol 185:441, 1956;.
12 +
deDuve, C., et al:  Tissue Fractionation Studies. 6. Intracellular Distribution Patterns of Enzymes in Rat-Liver Tissue , Biochem J 60:604, 1955;.
13 +
Appelmans, F.; Wattiaux, R.; and deDuve, C.:  Tissue Fractionation Studies: 5. The Association of Acid Phosphatase With a Special Class of Cytoplasmic Granules in Rat Liver , Biochem J 59:438, 1955;.
14 +
Malloy, H.T., and Evelyn, K.A.:  The Determination of Bilirubin With the Photoelectric Colorimeter , J Biol Chem 119:481, 1955;.
15 +
Odell, G.B.:  The Distribution of Bilirubin Between Albumin and Mitochondria , J Pediat 68:164, 1966;.
16 +
Weber, A.P., and Schalm, L.:  Quantitative Separation and Determination of Bilirubin and Conjugated Bilirubin in Human Serum , Clin Chem Acta 7:805, 1962;.
17 +
Stetten, M.R.:  Metabolism of Inorganic Pyrophosphate: 1. Microsomal Inorganic Pyrophosphate Phosphotransferase of Rat Liver , J Biol Chem 239: 3576, 1964;.
18 +
Smith, L.:  "Spectrophotometric Assay of Cytochrome C Oxidase,"  in Glick, D. (ed.): Methods of Biochemical Analysis , New York: Interscience Publishers, Inc., 1958;, vol II, p 427.
19 +
Barber-Riley, G.:  Measurement of Capacity of Biliary Tree in Rats , Amer J Physiol 205:1122, 1963;.
20 +
Matthews, C.M.E.; Bruce-Robertson, A.; and Humphrey, J.H.:  "Measurement of Extravascular Albumin in Normal Rabbits and Rats,"  in Plasma Proteins and Gastrointestinal Tract in Health and Disease , Baltimore: Williams & Wilkins Co., 1963;, p 36.
21 +
Dewey, W.C.:  Vascular-Extravascular Exchanges of I131-Plasma Proteins in the Rat , Amer J Physiol 197:423, 1959;.
22 +
Grodsky, G.M., et al:  Distribution of Bilirubin-H3 in the Fetal and Maternal Rat , Amer J Physiol 204:837, 1963;.
23 +
Dittmer, D.S., and Grebe, R.M. (eds.): Handbook of Circulation , Philadelphia: W. B. Saunders, Co., 1959;, pp 127, 129.
24 +
Martin, N.H.:  Preparation and Properties of Serum and Plasma Proteins: XXI. Interactions With Bilirubin , J Amer Chem Soc 71:1230, 1949;.
25 +
Klatskin, G., and Bungards, L.:  Bilirubin Protein Linkages in Serum and Their Relationship to the van den Bergh Reaction , J Clin Invest 35:537, 1956;.
26 +
Odell, G.B.:  Studies in Kernicterus. 1. The Protein Binding of Bilirubin , J Clin Invest 38:823, 1959;.
27 +
Lester, R., and Schmid, R.:  Bilirubin Metabolism , New Eng J Med 270:779, 1964;.
28 +
Stevenson, J.H., and Dutton, G.J.:  Glucuronide Synthesis in Kidney and Gastrointestinal Tract , Biochem J 82:330, 1962;.
29 +
Williamson, J.; Robinson, R.R.; and Owen, E.E.:  Mechanism of Bilirubin Excretion by Avian Kidney , Amer J Physiol 205:267, 1963;.
30 +
Schenker, S., and McCandless, D.W.:  Renal Disposition of Conjugated Bilirubin in Aglomerular Fish , Nature 202:1344, 1964;.
31 +
Fulop, M.; Sandson, J.; and Brazeau, P.:  Dialyzability, Protein Binding and Renal Excretion of Plasma Conjugated Bilirubin , J Clin Invest 44: 666, 1965;.
32 +
Odell, G.B.:  The Influence of pH on the Distribution of Bilirubin Between Albumin and Mitochondria , Proc Soc Exp Biol Med 120:352, 1965;.
33 +
Gartner, L.M., and Arias, J.M.:  Developmental Pattern of Glucuronide Formation in Rat and Guinea Pig Liver , Amer J Physiol 205:663, 1963;.
34 +
Dutton, G.J.; Langelaan, D.E.; and Ross, P.E.:  High Glucuronide Synthesis in Newborn Liver: Choice of Species and Substrate , Biochem J 93:4P, 1964;.
35 +
Boerth, R.D.; Blast, A.H.; and Spratt, J.T.:  Limitations in the Determination of in Vitro Bilirubin Glucuronide Formation , J Lab Clin Med 65: 475, 1965;.
36 +
Brown, A.K., and Zuelzer, W.W.:  Studies on Neonatal Development of Glucuronide Conjugating Systems , J Clin Invest 37:332, 1958;.

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