Main articles: Paracetamol toxicity and Analgesic nephropathy Excessive use of paracetamol can damage multiple organs, especially the liver and kidney. In both organs, toxicity from paracetamol is not from the drug itself but from one of its metabolites, N-acetyl-p-benzoquinoneimine (NAPQI). In the liver, the cytochrome P450 enzymes CYP2E1 and CYP3A4 are primarily responsible for the conversion of paracetamol to NAPQI. In the kidney, cyclooxygenases are the principal route by which paracetamol is converted to NAPQI.[50] Paracetamol overdose leads to the accumulation of NAPQI, which undergoes conjugation with glutathione. Conjugation depletes glutathione, a natural antioxidant. This in combination with direct cellular injury by NAPQI, leads to cell damage and death.[51]