Methanethiol metabolism and its role in the pathogenesis of hepatic encephalopathy in rats and dogs

Authors

  • Henk J. Blom,

    1. Division of Gastrointestinal and Liver Diseases, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands
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  • Robert A. F. M. Chamuleau,

    1. Department of Experimental Internal Medicine, Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands
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  • Jan Rothuizen,

    1. Department of Animal Medicine, University of Utrecht, 3508 TD Utrecht, The Netherlands
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  • Nicolaas E. P. Deutz,

    1. Department of Surgery, University of Maastricht, 6201 BX Maastricht, The Netherlands
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  • Dr. Albert Tangerman

    Corresponding author
    1. Division of Gastrointestinal and Liver Diseases, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands
    • Department of Medicine, Division of Gastrointestinal and Liver Diseases, University Hospital Nijmegen, Post Office Box 9101, 6500 HB Nijmegen, The Netherlands
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Abstract

The metabolism of methanethiol was studied in rats. Administration of a noncomatogenic dose of methanethiol through inspired air or injection into the upper colon resulted in an elevation of the concentrations of methanethiol mixed disulfides in serum (protein–S–S–CH3 and X–S–S–CH3, × yet unknown) and in urine (X–S–S–CH3. The concentrations of methanethiol mixed disulfides proved to be a relative measure of exposure to methanethiol. The levels of volatile sulfur compounds methanethiol, dimethylsulfide and dimethyldisulfide in the air expired by rats exposed to a noncomatogenic dose of methanethiol through the colon were also elevated. Rats with acute hepatic encephalopathy caused by liver ischemia also showed elevation of methanethiol mixed disulfide levels on challenge of methanethiol through the colon or inspired air, but to a significantly smaller extent than did the corresponding sham-operated rats. This suggests that the liver is at least partly responsible for formation of methanethiol mixed disulfides. No additional toxic effects were observed in the rats with ischemic livers on methanethiol exposition when compared with normal rats, suggesting that the liver does not play an essential role in methanethiol detoxification. Metabolism of methanethiol by blood to sulfate, for example, might be more important.

In rats with acute hepatic encephalopathy caused by liver ischemia and in dogs suffering from hepatic encephalopathy resulting from chronic liver disease, large and significant increases in ammonia levels were measured. However, the mean levels of methanethiol mixed disulfides in rats and dogs with hepatic encephalopathy were not different from the mean normal levels in these animals. It is concluded that in these animal models of liver failure the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor or insignificant.(HEPATOLOGY 1990; 11:682-689.)

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