Mitochondrial Permeability Transition in Pathogenesis of Hemorrhagic Injury: Targeted Therapy with Minocycline
Abstract
Patients that initially survive hemorrhage and resuscitation may develop a systemic inflammatory response syndrome (SIRS) that leads to injury and dysfunction of vital organs (multiple organ dysfunction syndrome, MODS), particularly to the liver and kidney. SIRS and MODS may involve mitochondrial dysfunction. Minocycline and doxycycline are tetracycline derivatives that are cytoprotective to liver, brain and other organs in various models of hypoxic, ischemic and oxidative stress, which may act by preserving mitochondrial function. We determined whether minocycline and doxycycline protect liver and kidney in a mouse model of hemorrhage and resuscitation. Minocycline and doxycycline each decreased liver enzymes and creatinine in the blood after hemorrhage/resuscitation compared to vehicle. Minocycline and doxycycline also significantly decreased liver necrosis and liver and kidney apoptosis. Lastly, minocycline protected against mitochondrial inner membrane permeabilization (mitochondrial permeability transition) occurring after HS/R and improved survival. In conclusion, minocycline and doxycycline when administered only after resuscitation decrease liver and kidney injury after hemorrhage/resuscitation and improve survival. These safe and widely used agents might be useful clinically to prevent SIRS and MODS after hemorrhagic shock.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2012
- Accession Number
- ADA591991
Entities
People
- John J. Lemasters
Organizations
- Medical University of South Carolina