Hepatic glutathione depletion
- Consumes hepatic glutathione
- Once glutathione is exhausted, the reactive metabolite attacks hepatocytes → hepatotoxicity
- The acetaminophen hepatotoxicity mechanism
- Cysteine repletion restores glutathione and blocks this step
Drugs with this mechanism (1)
- NAPQI — Reactive acetaminophen metabolite normally detoxified by glutathione; glutathione depletion permits severe liver injury.
Self-check
- What happens once hepatic glutathione is exhausted?
The reactive metabolite attacks hepatocytes. - What replenishment restores glutathione here?
Cysteine repletion.
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