Cuproptosis Is Induced in Drug-Induced Liver Injury by Oxidative Stress-Mediated Copper Overload - PubMed
5 hours ago
- #drug-induced liver injury
- #oxidative stress
- #cuproptosis
- Cuproptosis is a new cell death pathway induced by copper overload, characterized by proteotoxic stress.
- Drug-induced liver injury (DILI) from acetaminophen overdose induces cuproptosis via oxidative stress-mediated copper overload.
- Key cuproptosis-suppressive molecules (FDX1, lipoyl synthase, DLAT) decrease in DILI, leading to copper overload and liver damage.
- FDX1 knockdown worsens cuproptosis and liver injury in mice and cells.
- Copper deprivation (low-copper diet) reverses cuproptosis and liver injury, while high-copper diet exacerbates it.
- Oxidative stress relief (glutathione, Nrf2 activation) reduces copper accumulation, reverses cuproptosis, and alleviates DILI.
- Nrf2 activation is a promising therapeutic approach for DILI by inhibiting cuproptosis.