Cinnamtannin B-1, a natural antioxidant that reduces the effects of H 2 O 2 on CCK-8-evoked responses in mouse pancreati
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Cinnamtannin B-1, a natural antioxidant that reduces the effects of H2O2 on CCK-8-evoked responses in mouse pancreatic acinar cells Antonio Gonzalez & Patricia Santofimia-Castaño & Ramon Rivera-Barreno & Gines M. Salido
Received: 5 July 2011 / Accepted: 7 November 2011 / Published online: 26 November 2011 # University of Navarra 2011
Abstract This work was designed in order to gain an insight on the mechanisms by which antioxidants prevent pancreatic disorders. We have examined the properties of cinnamtannin B-1, which belongs to the class of polyphenols, against the effect of hydrogen peroxide (H2O2) in mouse pancreatic acinar cells. We have studied Ca2+ mobilization, oxidative state, amylase secretion, and cell viability of cells treated with cinnamtannin B-1 in the presence of various concentrations of H2O2. We found that H2O2 (0.1– 100 μM) increased CM-H2DCFDA-derived fluorescence, reflecting an increase in oxidation. Cinnamtannin B-1 (10 μM) reduced H2O2-induced oxidation of CM-H2DCFDA. CCK-8 induced oxidation of CMH2DCFDA in a similar way to low micromolar concentrations of H2O2, and cinnamtannin B-1 reduced A. Gonzalez : P. Santofimia-Castaño : G. M. Salido Department of Physiology (Cell Physiology Research Group), University of Extremadura, Caceres, Spain R. Rivera-Barreno Department of Medical Sciences, Institute of Biomedical Sciences, Autonomous University of Juarez, Ciudad Juarez, Mexico A. Gonzalez (*) Department of Physiology, Faculty of Veterinary Sciences, University of Extremadura, Avenida Universidad s/n, 10003 Caceres, Spain e-mail: [email protected]
the oxidant effect of CCK-8. In addition, H2O2 induced a slow and progressive increase in intracellular free Ca2+ concentration ([Ca2+]c). Cinnamtannin B-1 reduced the effect of H2O2 on [Ca2+]c, but only at the lower concentrations of the oxidant. H2O2 inhibited amylase secretion in response to cholecystokinin, and cinnamtannin B-1 reduced the inhibitory action of H2O2 on enzyme secretion. Finally, H2O2 reduced cell viability, and the antioxidant protected acinar cells against H2O2. In conclusion, the beneficial effects of cinnamtannin B-1 appear to be mediated by reducing the intracellular Ca2+ overload and intracellular accumulation of digestive enzymes evoked by ROS, which is a common pathological precursor that mediates pancreatitis. Our results support the beneficial effect of natural antioxidants in the therapy against oxidative stress-derived deleterious effects on cellular physiology. Keywords Exocrine pancreas . Calcium . Oxidative stress . Cinnamtannin B-1 . Hydrogen peroxide . Antioxidant
Introduction The exocrine pancreas is highly specialized in the synthesis, storage, and secretion of digestive enzymes. Gastrointestinal hormones, such as cholecystokinin (CCK), gastrin, neurotensin, and bombesin/gastrin-releasing peptide, are potent regulatory peptides that
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modulate pancreatic function [43, 47]. A rise in intracellular free Ca2+ concentration [Ca2+]c is an important early signal by which physiological secretagogues elicit the rel
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