Abstract
The Eisai hyperbilirubinemic rat is a mutant strain of Sprague-Dawley origin with hereditary defects in the biliary excretion of bilirubin glucuronide, glutathione, and several other organic anions. The correlation between bile flow and bile acid excretion rates during taurocholate infusion revealed that bile acid-independent flow was smaller in the mutant than in intact Sprague-Dawley rats (19.3 vs 56.0 μl/kg per min), while bile acid-dependent flow was similar. The correlation between bile flow and glutathione excretion rates in Sprague-Dawley rats with modified hepatic glutathione levels revealed that a certain portion of bile flow was proportional to the biliary excretion of glutathione, with a coefficient of 551 bile per 1 mol glutathione. One-third of bile acid-independent bile flow in intact Sprague-Dawley rats was accounted for by glutathione osmosis, which feature was absent in the mutant rats.
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References
Jansen PLM, Peters WH, Lamers WH. Hereditary chronic conjugated hyperbilirubinemia in mutant rats caused by defective hepatic anion transport. Hepatology 1985;5:573–579.
Oude Elferink RPJ, Ottenhoff R, Liefting W, et al. Hepatobiliary transport of glutathione and glutathione conjugate in rats with hereditary hyperbilirubinemia. J Clin Invest 1989;84:476–486.
Mikami T, Nozaki Y, Tagaya O, et al. The characteristics of a new mutant in rats with hyperbilirubinemia syndrome. Cong Anom 1986;26:250–251.
Takikawa H, Sano N, Narita T, et al. Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant Sprague-Dawley rat. Hepatology 1991;14:352–360.
Fernandez-Checa JC, Takikawa H, Horie T, et al. Canalicular transport of reduced glutathione in normal and mutant Eisai hyperbilirubinemic rats. J Biol Chem 1992;267:1667–1673.
Verkade HJ, Wolters H, Gerding A, et al. Mechanism of biliary lipid secretion in the rat: a role for bile acid-independent bile flow? Hepatology 1993;17:1074–1080.
Ballatori N, Truong AT. Relation between biliary glutathione excretion and bile acid-independent bile flow. Am J Physiol 1989;256:G22-G30.
Ballatori N, Truong AT. Glutathione as a primary osmotic driving force in hepatic bile formation. Am J Physiol 1992;263:G617-G624.
Ookhtens M, Hobdy K, Corvasce MC, et al. Sinusoidal efflux of glutathione in the perfused rat liver; evidence for a carriermediated process. J Clin Invest 1984;75:258–265.
Ballatori N, Jacob R, Boyer JL. Intrabiliary glutathione hydrolysis; a source of glutamate in bile. J Biol Chem 1986;264:7860–7865.
Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione; applications to mammalian blood and other tissues. Anal Biochem 1969;27:502–522.
Palmer RH. The enzymatic assay of bile acid and related 3α-hydroxysteroids; its application to serum and other biological fluids. Methods Enzymol 1969;XV:280–288.
Roda A, Hofmann AF, Mysels KJ. The influence of bile salt structure on self-association in aqueous solutions. J Biol Chem 1983;258:6362–6370.
Kaplowitz N, Eberle DE, Petrini J, et al. Factors influencing the efflux of hepatic glutathione into bile in rats. J Pharmacol Exp Ther 1983;224:141–147.
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Yoshida, H., Okano, Ki., Tamano, T. et al. Bile flow in a mutant Sprague-Dawley rat with defective biliary excretion of glutathione. J Gastroenterol 29, 439–442 (1994). https://doi.org/10.1007/BF02361240
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DOI: https://doi.org/10.1007/BF02361240