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Anti-Ischaemic Activity of S-Adenosyl-L-Methionine (SAMe) during Hypoxia/Reoxygenation in the Isolated Perfused Rat Liver

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Summary

In order to extend the limited data concerning the anti-ischaemic activity of S-adenosyl-L-methionine (SAMe), we evaluated the effect of SAMe in isolated perfused rat liver during and after normal-flow ischaemia (30 minutes) and reoxygenation (60 minutes). Application of SAMe 100 ¼mol/L in the perfusate suppressed (almost completely) the release of lactate dehydrogenase, alanine aminotransferase and sorbitol dehydrogenase into the perfusion medium. Furthermore, SAMe treatment resulted in substantial (44%) enhancement of bile flow and hepatic levels of glutathione and adenosine triphosphate compared with non-SAMe-treated livers, during both hypoxia and reoxygenation. Histological evaluation showed a marked reduction in the score for severity of liver necrosis with SAMe treatment (1.5 ± 0.5 vs 2.6 ± 0.3, score 0-4).

Thus, SAMe protects liver cells from ischaemic injury, possibly by restoring glutathione and adenosine triphosphate content. These findings may have clinical relevance for the preservation of organ function before and during transplantation.

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References

  • Blankenstein JD, Terpatra OT. Liver preservation: the past and the future. Hepatology 13: 1235–1250, 1991

    Article  Google Scholar 

  • Bray GP, Tredger JM, Williams R. S-Adenosylmethionine protects against acetaminophen hepatoxicity in two mouse models. Hepatology 15: 297–301, 1992

    Article  PubMed  CAS  Google Scholar 

  • Chawla RK, Bonkovsky HL, Galambos JT. Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver damage. Drugs 40: 98–110, 1990

    Article  PubMed  Google Scholar 

  • Corrales F, Gimenez A, Alvarez L, Caballeria J, Pajares MA, et al. S-adenosylmethionine treatment prevents CCl4-induced S-adenosylmethionine synthetase inactivation and attenuates liver injury. Hepatology 16: 1022–1027, 1992

    Article  PubMed  CAS  Google Scholar 

  • Frezza M, Surrenti C, Manzillo G, Fiaccadori F, Bortolini M, et al. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo controlled study. Gastroenterology 99: 211–215, 1990

    PubMed  CAS  Google Scholar 

  • Giulidori P, Galli-Kienle M, Catto E, Stramentinoli G. Trans-methylation, transsulfuration, and aminopropylation reactions of S-adenosyl-L-methionine in vivo. Journal of Biological Chemistry 259: 4205–4211, 1984

    PubMed  CAS  Google Scholar 

  • Jaeschke H, Mitchell JR. Use of isolated perfused organs in hy-poxia and ischemia/reperfusion oxidant stress. Methods in Enzymology 186: 752–759, 1990

    Article  PubMed  CAS  Google Scholar 

  • Lieber CS, Casini A, DeCarli LM, Kim CI, Lowe N, et al. S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatology 11: 165–172, 1990

    Article  PubMed  CAS  Google Scholar 

  • Maeda N, Kon K, Seklya M, Shiga T. Increase of ATP level in human erythrocytes induced by S-adenosyl-L-methionine. Biochemical Pharmacology 35: 625–695, 1986

    Article  PubMed  CAS  Google Scholar 

  • Matsui Y, Kubo Y, Iwata N. S-Adenosyl-L-methionine prevents ischemie neuronal death. European Journal of Pharmacology 144: 211–216, 1987

    Article  PubMed  CAS  Google Scholar 

  • Montero C, Smolenski RT, Duley JA, Simmonds HA. S-adenosyl-methionine increases erythrocyte ATP in vitro by a route independent of adenosine kinase. Biochemical Pharmacology 40: 2617–2623, 1990

    Article  PubMed  CAS  Google Scholar 

  • Sauter A. High performance liquid Chromatographic determination of adenine nucleotides in biological materials. Journal of Chromatography 325: 314–316, 1985

    Article  PubMed  CAS  Google Scholar 

  • Shaw BW, Wood RP. Improved results with retransplantation of the liver. Transplantation Proceedings 21: 2407–2408, 1989

    PubMed  Google Scholar 

  • Starzl TE, Demetris AJ, Van Thiel D. Liver transplantation. New England Journal of Medicine 321: 1014–1022, 1989

    Article  PubMed  CAS  Google Scholar 

  • Tietze P. Enzymic method for quantitative determination of nan-ograms amount of total and oxydized glutathione. Analytical Biochemistry 59: 502–522, 1969

    Article  Google Scholar 

  • Vendemiale G, Altomare F, Trizio T, Le Grazie C, Di Padova C, et al. Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scandinavian Journal of Gastroenterology 24: 407–415, 1989

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. BioResearch SpA, Via Fosse Ardeatine 2, 20060, Liscate, Milano, Italy

    H. Thom

  2. Knoll AG, Ludwigshafen, Germany

    M. Bortolini

  3. Department of Medical Chemistry and Biochemistry, University of Milan School of Medicine, Milan, Italy

    M. Galli-Kienle

Authors
  1. H. Thom
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  2. M. Bortolini
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  3. M. Galli-Kienle
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Thom, H., Bortolini, M. & Galli-Kienle, M. Anti-Ischaemic Activity of S-Adenosyl-L-Methionine (SAMe) during Hypoxia/Reoxygenation in the Isolated Perfused Rat Liver. Drug Invest 4 (Suppl 4), 64–68 (1992). https://doi.org/10.1007/BF03258365

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  • DOI: https://doi.org/10.1007/BF03258365

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