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Hepatic efflux and renal extraction of plasma glutathione: Marked differences between healthy subjects and the rat

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Summary

Hepatic efflux of glutathione accounts for almost 85% of the plasma level in the rat. However, the expected high concentration in the hepatic vein in man has not been demonstrated as yet. Our findings in ten patients without liver dysfunction reveal that substantial translocation of glutathione from the liver to the plasma does not occur. The removal rate of circulating glutathione by the kidney is far lower in man than in the rat (49.5% vs 84.6%). Moreover, the inferior vena cava in man contains more circulating glutathione than the artery, which is not consistent with the results obtained in the rat. Furthermore, the plasma concentration in man is about one tenth of that in the animals. These results clearly indicate that species-specific differences in the overall biosynthesis and metabolism of the tripeptide occur, resulting in marked variations in its plasma concentration.

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Abbreviations

GSH:

reduced glutathione

GSSG:

oxidized glutathione

GSH+GSSG:

glutathione — the sum of reduced and oxidized glutathione

Na4EDTA:

ethylenediamintetraacetic acid as its tetra-sodium salt

HCl:

hydrochloric acid

2-VP:

2-vinylpyridine

Τ-GT:

Τ-glutamyltranspeptidase

AT 125:

[αS, 5S]-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid

References

  1. Adams JD, Lauterburg BH, Mitchell JR (1983) Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress. J Pharm Exp Ther 227:749–754

    Google Scholar 

  2. Albert Z, Rzucidlo Z, Starzyk H (1970) Biochemical and histochemical investigations of the gamma-glutamyl-transpeptidase in embryonal and adult organs of man. Acta Histochem 37:74–79

    Google Scholar 

  3. Allen KGD, Arthur JR (1987) Inhibition by 5-sulfosalicylic acid of the GSH-reductase recycling assay for GSH analysis. Clin Chim Acta 162:237–239

    Google Scholar 

  4. Anderson M, Bridges RJ, Meister A (1980) Direct evidence for inter-organ transport of glutathione and that the nonfiltration renal mechanism for utilisation involvesρ-glutamyltranspeptidase. Biochem Biophys Res Comm 96:848–853

    Google Scholar 

  5. Anderson ME, Meister A (1980) Dynamic state of glutathione in blood plasma. J Biol Chem 255:9530–9533

    Google Scholar 

  6. Bartoli GM, Sies H (1978) Reduced and oxidized glutathione efflux from liver. FEBS Lett 86:89–91

    Google Scholar 

  7. Bartoli GM, HÄberle D, Sies H (1978) Glutathione efflux from perfused rat liver and its relation to glutathione uptake by the kidney. In: Sies H, Wendel A (eds) Functions of glutathione in liver and kidney. Springer, Berlin Heidelberg New York, pp 27–31

    Google Scholar 

  8. Beutler E, Gelbart T (1985) Plasma glutathione in health and in patients with malignant disease. J Lab Clin Med 105:581–584

    Google Scholar 

  9. Brehe JE, Burch HB (1976) Enzymatic assay for glutathione. Anal Biochem 74:184–197

    Google Scholar 

  10. Burgunder JM, Lauternburg BH (1987) Decreased production of glutathione in patients with cirrhosis. Eur J Clin Invest 17:408–414

    Google Scholar 

  11. Busachi C, Mebis J, Broeckaert L, Desmet V (1981) Histochemistry ofΤ-glutamyl transpeptidase in human liver biopsies. Path Res Pract 172:99–108

    Google Scholar 

  12. Chawla RK, Lewis FW, Kutner MH, Bate DM, Roy RGB, Rudman D (1984) Plasma cysteine, cystine, and glutathione in cirrhosis. Gastroenterology 87:770–776

    Google Scholar 

  13. Goldbarg JA, Friedman OM, Pineda EP, Smith EE (1960) The colorimetric determination ofΤ-glutamyl transpeptidase with a synthetic substrate. Arch Biochem Biophys 91:61–70

    Google Scholar 

  14. Griffith OW, Novogrodsky A, Meister A (1979) Translocation of GSH from lymphoid cells that have differentΤ-GT activities. Proc Natl Acad Sci USA 76:2249–2252

    Google Scholar 

  15. Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione-reductase and 2-vinylpyridine. Anal Biochem 106:207–212

    Google Scholar 

  16. Inoue M, Nobukuni Y, Ando Y, Hirota M (1986) Interorgan metabolism of glutathione as the defence mechanism against oxidative stress. In: Tanabe T (ed) Nephrotoxicity of antibiotics and immunosuppresants. Elsevier, Amsterdam New York, pp 52–67

    Google Scholar 

  17. Kaplowitz N, Aw TY, Ookhtens M (1985) The regulation of hepatic glutathione. Ann Rev Pharmacol Toxicol 25:715–744

    Google Scholar 

  18. Lunn G, Dale GL, Beutler E (1979) Transport accounts for glutathione turnover in human erythrocytes. Blood 54:238–244

    Google Scholar 

  19. Naftalin L, Sexton M, Whitaker JF, Tracey D (1969) A routine procedure for estimating serumΤ-glutamyl transpeptidase activity. Clin Chim Acta 26:293–252

    Google Scholar 

  20. Ookhtens M, Hobdy K, Corvasce MC, Aw TY, Kaplowitz N (1985) Sinusoidal efflux of glutathione in the perfused rat liver. J Clin Invest 75:258–265

    Google Scholar 

  21. Ronchi G, Desmet VJ (1973) Histochemical study ofΤ-glutamyl transpeptidase in experimental intrahepatic and extrahepatic cholestasis. Beitr Path 150:316–321

    Google Scholar 

  22. Wernze H (1970) Einfache Technik zur Katheterisierung der V. hepatica bei der Ratte in situ. Z Gesamte Exp Med 153:234–236

    Google Scholar 

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Authors and Affiliations

  1. Medizinische UniversitÄts-Klinik, Würzburg

    E. Purucker & H. Wernze

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  1. E. Purucker
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  2. H. Wernze
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Purucker, E., Wernze, H. Hepatic efflux and renal extraction of plasma glutathione: Marked differences between healthy subjects and the rat. Klin Wochenschr 68, 1008–1012 (1990). https://doi.org/10.1007/BF01646546

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  • DOI: https://doi.org/10.1007/BF01646546

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