Methanethiol Metabolism and Its Role in the Pathogenesis of Hepatic Encephalopathy in Rats and Dogs

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, X 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Volatile metabolites in occupational exposure to organic sulfur compounds

“…Less is known again of the chemical nature of the mixed disulfides (Blom et al 1990). They are synthesized in the liver (Blom et al 1990), presenting probably the major pathway of methanethiol metabolism.…”

“…1) include, e.g. formic acid, sulfate (Blom and Tangerman 1988) and mixed disulfides (Blom et al 1990). Although methods exist for the urinalysis of formic acid (Liesivuofi and Savolainen 1987) it is not certain whether methyl mercaptan-derived formate could be detected in view of the inhaled doses and endogenous formate present also in the control urines.…”

“…They are synthesized in the liver (Blom et al 1990), presenting probably the major pathway of methanethiol metabolism. In the case of liver disease or dysfunction, methionine loading causes a significant increase in blood methanethiol and dimethyl sulfide concentrations (A1 Mardini et al 1988).…”

“…The oxidation may also take place in the liver as CHaSH is also a ligand for the mixed function oxidase (Dawson et al 1983). The most important metabolic pathway is probably the formation of mixed disulfides (R-S-S-CH3) in the liver (Blom et al 1990), while methylation produces the exhalable dimethyl sulfide (CH3-S-CH3)…”

Volatile Sulfur Production by Pig Cecal Bacteria in Batch Culture and Screening Inhibitors of Sulfate Reducing Bacteria.

“…Hydrogen sulfide might also injure colonocytes (2) and be responsible for ulcerative colitis (3,4) and colon cancer (5). Methanethiol produced from methio nine by intestinal bacteria may cause hepatic en cephalopathy in rats, dogs (6,7), and cirrhosis patients. Therefore it is important to develop ingestible agents to control intestinal sulfide generation in mammals, with minimal toxicity.…”