title: Cinnamtannin B-1, a natural antioxidant that reduces the effects of H(2)O(2) on CCK-8-evoked responses in mouse pancreatic acinar cells.
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 (H(2)O(2)) in mouse pancreatic acinar cells. We have studied Ca(2+) mobilization, oxidative state, amylase secretion, and cell viability of cells treated with cinnamtannin B-1 in the presence of various concentrations of H(2)O(2). We found that H(2)O(2) (0.1-100 μM) increased CM-H(2)DCFDA-derived fluorescence, reflecting an increase in oxidation. Cinnamtannin B-1 (10 μM) reduced H(2)O(2)-induced oxidation of CM-H(2)DCFDA. CCK-8 induced oxidation of CM-H(2)DCFDA in a similar way to low micromolar concentrations of H(2)O(2), and cinnamtannin B-1 reduced the oxidant effect of CCK-8. In addition, H(2)O(2) induced a slow and progressive increase in intracellular free Ca(2+) concentration ([Ca(2+)](c)). Cinnamtannin B-1 reduced the effect of H(2)O(2) on [Ca(2+)](c), but only at the lower concentrations of the oxidant. H(2)O(2) inhibited amylase secretion in response to cholecystokinin, and cinnamtannin B-1 reduced the inhibitory action of H(2)O(2) on enzyme secretion. Finally, H(2)O(2) reduced cell viability, and the antioxidant protected acinar cells against H(2)O(2). In conclusion, the beneficial effects of cinnamtannin B-1 appear to be mediated by reducing the intracellular Ca(2+) 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.
authors: Department of Physiology (Cell Physiology Research Group), University of Extremadura, Caceres, Spain. agmateos@unex.es
authors: Antonio
authors: A
authors: Gonzalez
authors: Patricia
authors: P
authors: Santofimia-Castaño
authors: Ramon
authors: R
authors: Rivera-Barreno
authors: Gines M
authors: GM
authors: Salido
mesh_terms: D061354:Acinar Cells / Q000187:drug effects* / Q000378:metabolism; D000681:Amylases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010179:Pancreas / Q000166:cytology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D012844:Sincalide / Q000502:physiology*
chemical_list: D000975:Antioxidants; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016877:Oxidants; D044945:Proanthocyanidins; C517872:cinnamtannin B-1; D006861:Hydrogen Peroxide; D000681:Amylases; D012844:Sincalide