Oxidative Stress and Apoptosis Inhibition Mitigate Static Cold Storage-Induced Injury in Liver Sinusoidal Endothelial...

Area of Science:

• Organ transplantation
• Cellular injury mechanisms
• Preservation science

Background:

• Donor liver scarcity is a major challenge in transplantation.
• Ischemia-reperfusion injury (IRI) during organ preservation reduces liver utilization.
• Liver sinusoidal endothelial cells (LSECs) are key mediators of IRI, but their response to preservation is unclear.

Purpose of the Study:

• To investigate the impact of static cold storage (SCS) on isolated rat LSECs.
• To assess LSEC viability, functionality, morphology, and gene expression after SCS.
• To evaluate the efficacy of inhibiting apoptosis and oxidative stress in LSECs during SCS.

Main Methods:

• Isolated rat LSECs were subjected to up to 3 days of SCS.
• Cell viability, metabolic activity, ATP levels, and reactive oxygen species (ROS) production were measured.
• Gene expression related to oxidative stress and apoptosis was analyzed.
• LSECs were treated with apoptosis and/or oxidative stress inhibitors.

Main Results:

• SCS reduced LSEC viability by ~40% and metabolic activity/ATP by ~60%.
• SCS doubled ROS production and upregulated oxidative stress/apoptosis genes in LSECs.
• Combined inhibition of apoptosis and oxidative stress improved LSEC viability by 20% and metabolic activity/ATP by 30-40%, reducing ROS by 50%.

Conclusions:

• LSECs are highly vulnerable to preservation injury from SCS.
• Targeting LSEC-specific injury pathways is crucial for improving organ preservation.
• Developing endothelial-targeted strategies can enhance liver transplantation success rates.