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S-Adenosyl-L-Methionine Prevents Intracellular Glutathione Depletion by GSH-Depleting Drugs in Rat and Human Hepatocytes

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Summary

This study examines the ability of externally added S-adenosyl-L-methionine (SAMe) to act as a precursor of intracellular glutathione (GSH) and to prevent the GSH depletion induced by paracetamol, opiates and ethanol in rat and human hepatocytes.

Incubation of rat or human hepatocytes with SAMe 100 μmol/L as the only sulphur source in the medium resulted in a time-dependent elevation of intracellular GSH. Pretreatment of hepatocytes with SAMe resulted in a significant decrease in the cytotoxicity produced by exposure to paracetamol, heroin, methadone or ethanol, when compared with cultures not pretreated with SAMe. Preincubation of rat and human hepatocytes with SAMe attenuated the GSH depletion caused by paracetamol, heroin and methadone. In addition, the decrease in GSH resulting from exposure of hepatocytes to ethanol 50 mmol/L was prevented when SAMe was simultaneously added to cultures.

These experimental results provide direct evidence that exogenously administered SAMe increases intracellular GSH levels in rat and human hepatocytes and prevents the GSH depletion caused by paracetamol, opiates and ethanol.

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Authors and Affiliations

  1. Unidad de Hepatología Experimental, Centro de Investigación Hospital, Universitario ‘La Fe’, Avda Campanar 21, E-46009, Valencia, Spain

    R. Jover, X. Ponsoda, M. J. Gómez-Lechón & J. V. Castell

  2. Servicio de Cirugía General, A. Hospital General de Valencia, Valencia, Spain

    R. Fabra & R. Trullenque

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  1. R. Jover
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  2. X. Ponsoda
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  3. R. Fabra
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  4. R. Trullenque
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  5. M. J. Gómez-Lechón
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  6. J. V. Castell
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Jover, R., Ponsoda, X., Fabra, R. et al. S-Adenosyl-L-Methionine Prevents Intracellular Glutathione Depletion by GSH-Depleting Drugs in Rat and Human Hepatocytes. Drug Invest 4 (Suppl 4), 46–53 (1992). https://doi.org/10.1007/BF03258363

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