查看文章

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury. Compensatory liver regeneration is crucial for the final outcome of toxicant-induced injury. However, the molecular mechanisms underlying compensatory liver regeneration in mice after APAP-induced liver injury are not completely understood. This study aimed to investigate the role of dynamic and coordinated regulation of Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid 2–related factor 2 (NRF2)– antioxidant response element (ARE) and p53/p21 pathways in APAP injury-responsive liver regeneration. We found that mice exhibited massive hepatic toxicity during the first 12 hours after 400 mg/kg APAP treatment, but responsive liver recovery occurred beyond 24 hours as demonstrated by histopathological and biochemical assessments. The expression and nuclear accumulation of NRF2 was increased after …