N-Acetylcysteine (NAC) is given in paracetamol (acetaminophen) overdose. Which mechanism explains its hepatoprotective action?

• A NAC directly inhibits CYP2E1 and CYP3A4, preventing formation of NAPQI
• B NAC chelates NAPQI directly in the bloodstream, forming a stable non-toxic complex
• C NAC activates UGT and sulfotransferase enzymes to increase Phase II conjugation of paracetamol
• D NAC is a cysteine precursor for glutathione (GSH) synthesis, replenishing hepatic GSH that conjugates NAPQI to prevent protein adduct formation ✓

Explanation

Paracetamol is metabolised by CYP2E1 (and CYP3A4) to NAPQI (N-acetyl-p-benzoquinone imine), a reactive electrophile. Normally, NAPQI is conjugated with glutathione (GSH) to form a non-toxic mercapturic acid conjugate. In overdose, hepatic GSH is depleted and NAPQI covalently binds cysteine residues of cellular proteins, causing necrosis. NAC acts primarily by providing cysteine (after hydrolysis to cysteine) for GSH resynthesis, replenishing hepatic GSH stores. NAC also acts as a direct antioxidant and anti-inflammatory, but GSH replenishment is the primary mechanism.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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