Possible Interaction: Acetaminophen and Cysteine

“The data indicate that therapeutic doses of acetaminophen markedly stimulate the rate of turnover of the pool of cysteine available for the synthesis of GSH, most likely due to an increased rate of synthesis of GSH which is required to detoxify the toxic metabolite of acetaminophen.”

“The addition of Cys to APAP cures decreased plasma alanine transaminase (P<0·05), the fractional synthesis rate of liver proteins (P<0·01), and increased masses of extensor digitorum longus (P<0·01), and soleus (P<0·05), compared with the APAP group.”

“ Cysteine availability could become limiting under repeated cures with APAP , especially when food intake is suboptimal.”

“Hence, without dietary sulphur amino acid increase, peripheral bioavailability of Cys and muscle GSH are potential players in the control of muscle mass under chronic treatment with APAP , an analgesic medication of widespread use, especially in the elderly.”

“ Acetaminophen (500 mg/kg) decreased embryonic and VYS cysteine content by 54% and 83%, respectively, after 24 h. Acetaminophen alters the spatial distribution of LMWT in rat conceptuses, particularly with respect to cysteine.”

“ APAP administration depleted the kidney GSH and Cys contents in a dose- and time-dependent manner.”

“The dose-dependent depletion of GSH, the trend toward an increase in ACAP-GSH-derived conjugate … GSH depletion by providing dietary methionine in excess of requirement indicate that prolonged ingestion of ACAP may increase the requirement for sulfur-… limit the availability of methionine and cysteine for protein … drug detoxification.”

“The effect of ACM on Cd redistribution was antagonized by administration of cysteine , a glutathione precursor, and was enhanced by pretreatment with phenobarbital, a potent inducer of the cytochrome P-450 mixed-function oxidase system.”

“The L-cysteine pro-drugs increased the urinary excretion of the cysteine and mercapturic acid conjugates of acetaminophen (34-119%) but did not alter excretion of acetaminophen-glucuronide or acetaminophen-sulfate.”

“decreased the formation of the mercapturate and cysteine conjugates of acetaminophen , the depletion of glutathione and the in vivo covalent binding of an acetaminophen metabolite to hepatic proteins and prevented the increase in serum glutamic-pyruvic transaminase activity, the appearance of liver lesions and mortality.”