Evaluation of peripheral blood mitochondrial function in experimental and clinical acute pancreatitis

Abstract

Background: Mitochondrial dysfunction occurs in the pancreas and in extra-pancreatic organs early in experimental acute pancreatitis (AP). However, direct measurement of mitochondrial function (MtF) within these organs is not possible in clinical settings. Aims: To measure and describe changes in MtF in peripheral blood in experimental and clinical AP. Patients & methods: MtF was measured in peripheral blood mononuclear cells (PBMC) bymeasuringoxygenflux through the electron transport system(ETS) in anexperimental anda clinical study.MeasurementofMtFwas done in rats (n1⁄418) with caerulein induced mild AP (CAP) and in patients (n1⁄418) admittedwith predictedmild tomoderate AP. In both studiesMtFwas compared with appropriate controls. Mitochondrial superoxide production, cytochrome c, mitochondrial membrane potential (âˆy a a), and adenine triphosphate (ATP) were also measured in the clinical study. Results: MtF was successfully measured in the PBMC fraction of blood. The most significant alteration in MtF was increased endogenous respiration and leak respiration in both studies. The clinical study also revealed significant increases in mitochondrial superoxide and mitochondrial membrane potential and a decrease in cytochrome c but no change in total cell ATP content. Conclusion: This is the first study tomeasure changes in peripheral blood MtF inAP.MtF inPBMCwasaltered inboth theexperimental andclinical acute pancreatitis settings. Further studies should now investigate the time course of peripheral changes in MtF to explore whether it correlates with disease severity, end organ dysfunction and as an outcome predictor in AP.