Effects of methionine and other sulfur compounds on drug conjugations

Metabonomics evaluation of urine from rats given acute and chronic doses of acetaminophen using NMR and UPLC/MS

“…The UPLC/MS spectra showed that many antioxidants in urine were lowered significantly which gives new insight into antioxidant protective mechanisms in the liver of rodents in addition to the previously published role of the antioxidants glutathione and Nacetylcysteine [44][45][46][47]. The analyses and spectral changes reported in this manuscript are in agreement with the recent COMET model of 80 toxins that correctly predicted the acute APAP study as hepatotoxic while chronic dosing with APAP was not classified as hepatotoxic [48].…”

Nutritional toxicology: Basic principles and actual problems

“…The decreases in available sulphate and GSH during sulphur amino acid deficiency cause decreased ACAP conjugation, increased adduct formation and increased hepatotoxicity (Reicks and Hathcock 1988a). Similar effects of decreased methionine/cystine intake have been observed for other toxicants , Rowe et al 1986).…”

Effects of Long-Term Administration of Acetaminophen on the Nutritional Utilization of Dietary Protein

“…Malnutrition has been asso ciated with decreased ACAP conjugation in the rat [18. 19] and in the mouse [9], as well as with increased ACAP hepatotoxicity in mice [20] and humans. In a very recent review of Hathcock [21] about the metabolic depletion of nutrients by drugs, it has been pointed out that increased utilization of sul fate and GSH in detoxification of prolonged ACAP ingestion leads to methionine defi ciency in mice when sulfur amino acid in take is marginal, concluding that methionine requirement under these conditions is in creased.…”

“…ACAP. which is often con sumed in multiple-gram daily doses, can po tentially induce methionine deficiency through depletion of sulfate and glutathione (GSH) [8], ACAP doses in humans are rec ommended up to 4 g. and about 50% of this dose is conjugated by sulfate or GSH [9], Therefore, chronic ACAP consumption could result in methionine deficiency if sul fur amino acid intake is marginal. Previous studies [8,10,11] have shown that pro longed ACAP administration induces methi onine deficiency in methionine marginal an imals, as indicated by decreased growth, in hibition of protein synthesis and decreases in tissue GSH levels [9, 10.…”