Mitochondrial dysfunction in peripheral blood mononuclear cells in early experimental and clinical acute pancreatitis

作者：Chakraborty Mandira^*; Hickey Anthony J R; Petrov Maxim S; Macdonald Julia R; Thompson Nichola; Newby Lynette; Sim Dalice; Windsor John A; Phillips Anthony R J

来源：Pancreatology, 2016, 16(5): 739-747.

DOI：10.1016/j.pan.2016.06.659

• Peripheral blood mononuclear cells
• Electron transport system
• Mitochondrial membrane potential
• Adenine triphosphate
• Oxidative stress

Background/objectives: Mitochondrial dysfunction occurs in vital organs in experimental acute pancreatitis (AP) and may play an important role in determining severity of AP. However, obtaining vital organ biopsies to measure mitochondrial MtF) in patients with AP poses considerable risk of harm. Being able to measure MtF from peripheral blood will bypass this problem. Furthermore, whether mitochondrial dysfunction is detectable in peripheral blood in mild AP is unknown. Therefore, the objective was to evaluate peripheral blood MtF in experimental and clinical AP.
Method: Mitochondrial respiration was measured using high resolution oxygraphy in an experimental study in caerulein induced AP and in a separate study, in patients with mild AR Superoxide, cytochrome c, mitochondrial membrane potential (Delta Psi) and adenine triphosphate (ATP) were also measured as other markers of MtF.
Results: Even though some states of mitochondrial respiration were increased in both experimental and clinical AP, this did not lead to an increase in net ATP in patients with AP. The increased leak respiration in both studies was further proof of dyscoupled mitochondria. In the clinical study there were also features of mitochondrial dysfunction with increased leak flux control ratio, superoxide, Delta Psi and decreased cytochrome c.
Conclusion: There is evidence of mitochondrial dysfunction with dyscoupled mitochondria, increased superoxide and decreased cytochrome c in patients with mild acute pancreatitis. Further studies should now determine whether mitochondrial function alters with severity in AP and whether mitochondrial dysfunction responds to treatments.

• 出版日期2016-10