Yes there is good evidence that acetaminophen (the active ingredient in Tylenol) can deplete glutathione under certain conditions. But whether that matters depends on dose, duration, and individual factors. Sex differences in glutathione metabolism and acetaminophen toxicity Acetaminophen detoxification in cucumber plants via induction of glutathione S transferases ScienceDirect Metabolic activation of acetaminophen. 85 90% of APAP is primarily Download Scientific Diagram Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential ScienceDirect