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.