Effects of the mitochondria-targeted antioxidant mitoquinone in murine acute pancreatitis.

TitleEffects of the mitochondria-targeted antioxidant mitoquinone in murine acute pancreatitis.
Publication TypeJournal Article
Year of Publication2015
AuthorsHuang, W, Cash, N, Wen, L, Szatmary, P, Mukherjee, R, Armstrong, J, Chvanov, M, Tepikin, AV, Murphy, MP, Sutton, R, Criddle, DN
JournalMediators Inflamm
Volume2015
Pagination901780
Date Published2015
ISSN1466-1861
KeywordsAcinar Cells, Acute Disease, Animals, Antioxidants, Apoptosis, Ceruletide, Cholecystokinin, Disease Models, Animal, Inflammation, Male, Membrane Potential, Mitochondrial, Mice, Mitochondria, Necrosis, Organophosphorus Compounds, Oxidative Stress, Pancreas, Pancreatitis, Reactive Oxygen Species, Taurolithocholic Acid, Ubiquinone
Abstract

Although oxidative stress has been strongly implicated in the development of acute pancreatitis (AP), antioxidant therapy in patients has so far been discouraging. The aim of this study was to assess potential protective effects of a mitochondria-targeted antioxidant, MitoQ, in experimental AP using in vitro and in vivo approaches. MitoQ blocked H2O2-induced intracellular ROS responses in murine pancreatic acinar cells, an action not shared by the control analogue dTPP. MitoQ did not reduce mitochondrial depolarisation induced by either cholecystokinin (CCK) or bile acid TLCS, and at 10 µM caused depolarisation per se. Both MitoQ and dTPP increased basal and CCK-induced cell death in a plate-reader assay. In a TLCS-induced AP model MitoQ treatment was not protective. In AP induced by caerulein hyperstimulation (CER-AP), MitoQ exerted mixed effects. Thus, partial amelioration of histopathology scores was observed, actions shared by dTPP, but without reduction of the biochemical markers pancreatic trypsin or serum amylase. Interestingly, lung myeloperoxidase and interleukin-6 were concurrently increased by MitoQ in CER-AP. MitoQ caused biphasic effects on ROS production in isolated polymorphonuclear leukocytes, inhibiting an acute increase but elevating later levels. Our results suggest that MitoQ would be inappropriate for AP therapy, consistent with prior antioxidant evaluations in this disease.

DOI10.1155/2015/901780
Alternate JournalMediators Inflamm.
Citation Key10.1155/2015/901780
PubMed ID25878403
PubMed Central IDPMC4386569
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom
/ / Biotechnology and Biological Sciences Research Council / United Kingdom