Mandira Chakraborty1, Anthony J R Hickey2, Maxim S Petrov3, Julia R Macdonald3, Nichola Thompson3, Lynette Newby4, Dalice Sim5, John A Windsor3, Anthony R J Phillips6. 1. Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, New Zealand. Electronic address: mandira.chakraborty@gmail.com. 2. School of Biological Sciences, Faculty of Science, University of Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, New Zealand. 3. Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, New Zealand. 4. Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand. 5. School of Mathematics, Statistics and Operations Research, Victoria University of Wellington, Wellington, New Zealand. 6. 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.
Abstract
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 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. 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 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. 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.
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 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. 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 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. 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.
Authors: Yaroslav M Susak; Olexandr O Dirda; Olexandr G Fedorchuk; Olekcandr A Tkachenko; Larysa M Skivka Journal: Dig Dis Sci Date: 2020-03-13 Impact factor: 3.199
Authors: Jack C Morton; Jane A Armstrong; Ajay Sud; Alexei V Tepikin; Robert Sutton; David N Criddle Journal: J Clin Med Date: 2019-12-13 Impact factor: 4.241
Authors: Katalin Márta; Anikó N Szabó; Dániel Pécsi; Péter Varjú; Judit Bajor; Szilárd Gódi; Patrícia Sarlós; Alexandra Mikó; Kata Szemes; Mária Papp; Tamás Tornai; Áron Vincze; Zsolt Márton; Patrícia A Vincze; Erzsébet Lankó; Andrea Szentesi; Tímea Molnár; Roland Hágendorn; Nándor Faluhelyi; István Battyáni; Dezső Kelemen; Róbert Papp; Attila Miseta; Zsófia Verzár; Markus M Lerch; John P Neoptolemos; Miklós Sahin-Tóth; Ole H Petersen; Péter Hegyi Journal: BMJ Open Date: 2017-09-14 Impact factor: 2.692
Authors: Christopher P Hedges; Toan Pham; Bhoopika Shetty; Stewart W C Masson; Anthony J R Hickey; Peter R Shepherd; Troy L Merry Journal: Biosci Rep Date: 2020-10-30 Impact factor: 3.840