Dexmedetomidine ameliorates hepatic ischemia reperfusion injury via modulating SIRT3 mediated mitochondrial quality control.

Ischaemia-reperfusion (IR) damage is an inevitable adverse effect of liver surgery. Recent research has found that IR damage is involved in severe mitochondrial dysfunction. Mitochondrial biosynthesis and dynamics control mitochondrial mass, distribution, and function. Sirtuin 3 (SIRT3) is widely known for preserving health and functionality of mitochondria. DEX has been proven to alleviate liver damage through antioxidant and anti-apoptotic pathways. But it's unclear how DEX protects mitochondria at this time. In this research, the mechanism behind the protective benefits of DEX was examined using the rat liver IR model and the rat liver cells (BRL-3 A) hypoxia reoxygenation (HR) model. We discovered that DEX treatment restored mitochondrial membrane potential, promoted ATP production, prevented oxidative stress, and decreased apoptosis in BRL-3 A cells. Furthermore, HR damage increased mitochondrial fission while decreasing mitochondrial fusion and biogenesis in BRL-3 A cells, which DEX partially corrected. The benefits of DEX on mitochondrial protection were reversed after addition of SR-18,292. Additionally, DEX showed the ability to enhance SIRT3 expression, and after cells were transfected with SIRT3 siRNA, DEX's effects on mitochondria were partially prevented. Similarly, in the rat model, DEX alleviating liver histopathological injury and oxidative stress. DEX inhibited IR-induced mitochondrial damage through improving ETC complex I- IV activities and ATP content, reducing apoptosis, controlling mitochondrial quality, and upregulating the expression of SIRT3. Additionally, our research shows that DEX's ability to protect the liver against IR damage is mediated by the modulation of mitochondrial quality control. Overall, the modification of SIRT3 activity could be responsible for this outcome.