Mitochondrial Permeability Transition in Pathogenesis of Hemorrhagic Injury: Targeted Therapy with Minocycline
Revised final rept. 1 Jul 2009-31 Dec 2011
MEDICAL UNIV OF SOUTH CAROLINA CHARLESTON
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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 hemorrhageresuscitation 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 HSR and improved survival. In conclusion, minocycline and doxycycline when administered only after resuscitation decrease liver and kidney injury after hemorrhageresuscitation and improve survival. These safe and widely used agents might be useful clinically to prevent SIRS and MODS after hemorrhagic shock.
- Medicine and Medical Research