title: Beneficial effect of the bioflavonoid quercetin on cholecystokinin-induced mitochondrial dysfunction in isolated rat pancreatic acinar cells.
abstract: The pathogenesis of acute pancreatitis (AP) is still poorly understood. Thus, a reliable pharmacological therapy is currently lacking. In recent years, an impairment of the energy metabolism of pancreatic acinar cells, caused by Ca(2+)-mediated depolarization of the inner mitochondrial membrane and a decreased ATP supply, has been implicated as an important pathological event. In this study, we investigated whether quercetin exerts protection against mitochondrial dysfunction. Following treatment with or without quercetin, rat pancreatic acinar cells were stimulated with supramaximal cholecystokinin-8 (CCK). CCK caused a decrease in the mitochondrial membrane potential (MMP) and ATP concentration, whereas the mitochondrial dehydrogenase activity was significantly increased. Quercetin treatment before CCK application exerted no protection on MMP but increased ATP to a normal level, leading to a continuous decrease in the dehydrogenase activity. The protective effect of quercetin on mitochondrial function was accompanied by a reduction in CCK-induced changes to the cell membrane. Concerning the molecular mechanism underlying the protective effect of quercetin, an increased AMP/ATP ratio suggests that the AMP-activated protein kinase system may be activated. In addition, quercetin strongly inhibited CCK-induced trypsin activity. The results indicate that the use of quercetin may be a therapeutic strategy for reducing the severity of AP.
authors.affiliation: a Institute of Clinical Chemistry and Laboratory Medicine, University of Rostock, Ernst-Heydemann-Straße 6, 18057 Rostock, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Weber
authors.forename: Ludwig
authors.initials: L
authors.lastname: Jonas
authors.forename: Michael
authors.initials: M
authors.lastname: Wakileh
authors.forename: Burkhard
authors.initials: B
authors.lastname: Krüger
mesh_terms: D061354:Acinar Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010088:Oxidoreductases / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D014357:Trypsin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D010446:Peptide Fragments; C410885:cholecystokinin 8; D000255:Adenosine Triphosphate; D002766:Cholecystokinin; D011794:Quercetin; D010088:Oxidoreductases; D010196:Pancreatic Elastase; D014357:Trypsin