title: Mitochondrial dysfunction in peripheral blood mononuclear cells in early experimental and clinical acute pancreatitis.
abstract: OBJECTIVE
  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 function (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.
  
  
  METHODS
  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 AP. Superoxide, cytochrome c, mitochondrial membrane potential (ΔΨ) 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, ΔΨ and decreased cytochrome c.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, New Zealand. Electronic address: mandira.chakraborty@gmail.com.
authors.forename: Mandira
authors.initials: M
authors.lastname: Chakraborty
authors.affiliation: School of Biological Sciences, Faculty of Science, University of Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, New Zealand.
authors.forename: Anthony J R
authors.initials: AJ
authors.lastname: Hickey
authors.affiliation: Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
authors.forename: Maxim S
authors.initials: MS
authors.lastname: Petrov
authors.affiliation: Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Macdonald
authors.affiliation: Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
authors.forename: Nichola
authors.initials: N
authors.lastname: Thompson
authors.affiliation: Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Lynette
authors.initials: L
authors.lastname: Newby
authors.affiliation: School of Mathematics, Statistics and Operations Research, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Dalice
authors.initials: D
authors.lastname: Sim
authors.affiliation: Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
authors.forename: John A
authors.initials: JA
authors.lastname: Windsor
authors.affiliation: Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, New Zealand; School of Biological Sciences, Faculty of Science, University of Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, New Zealand.
authors.forename: Anthony R J
authors.initials: AR
authors.lastname: Phillips
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D002108:Ceruletide; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D002108:Ceruletide; D000255:Adenosine Triphosphate; D045304:Cytochromes c
keywords: Adenine triphosphate; Electron transport system; Mitochondrial membrane potential; Oxidative stress; Peripheral blood mononuclear cells