Mitochondrial dysfunction in peripheral blood mononuclear cells in early experimental and clinical acute pancreatitis
| Autor: | Julia R. MacDonald, Mandira Chakraborty, Dalice Sim, Anthony J. R. Hickey, John A. Windsor, Anthony R. J. Phillips, Lynette Newby, Nichola M. Thompson, Maxim S. Petrov |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Pathology Mitochondrial Diseases Endocrinology Diabetes and Metabolism Mitochondrion medicine.disease_cause Peripheral blood mononuclear cell Monocytes 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate Oxygen Consumption Superoxides Internal medicine Respiration Animals Humans Medicine Rats Wistar Aged Membrane Potential Mitochondrial Membrane potential Hepatology biology Superoxide business.industry Cytochrome c Gastroenterology Cytochromes c Middle Aged medicine.disease Rats Oxidative Stress 030104 developmental biology Endocrinology Pancreatitis chemistry Acute Disease biology.protein Acute pancreatitis Female business Ceruletide Oxidative stress |
| Zdroj: | Pancreatology. 16:739-747 |
| ISSN: | 1424-3903 |
| DOI: | 10.1016/j.pan.2016.06.659 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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