Antioxidant and Prooxidant Effects of Phenolics on Pancreatic β-Cells in Vitro

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Abstract
A number of natural phenolic compounds display antioxidant and cell protective effects in cell culture models, yet in some studies show prooxidant and cytotoxic effects. Pancreatic β-cells have been reported to exhibit particular sensitivity to oxidative stress, a factor that may contribute to the impaired β-cell function characteristic of diabetes. The aim of this study was to examine the potential of natural phenolics to protect cultured pancreatic β-cells (βTC1 and HIT) from H2O2 oxidative stress. Exposure of cells to H2O2 led to significant proliferation inhibition. Contrary to what one should expect, simultaneous exposure to H2O2 and the phenolics, quercetin (10−100 μM), catechin (50−500 μM), or ascorbic acid (100−1000 μM), led to amplification of proliferation inhibition. At higher concentrations, these compounds inhibited proliferation, even in the absence of added H2O2. This prooxidant effect is attributable to the generation of H2O2 through interaction of the added phenolic compounds with as yet undefined componenets of the culture media. On the other hand, inclusion of metmyoglobin (30 μM) in the culture medium significantly reduced the prooxidant impact of the phenolics. Under these conditions, quercetin and catechin significantly protected the cells against oxidative stress when these components were present during the stress period. Furthermore, significant cell protection was observed upon preincubation of cells with chrysin, quercetin, catechin, or caffeic acid (50 μM, each) prior to application of oxidative stress. It is concluded that provided artifactual prooxidant effects are avoided, preincubation of β-cells with relatively hydrophobic natural phenolics can confer protection against oxidative stress. Keywords: Pancreatic β-cells; phenolics; flavonoids; oxidative stress; antioxidants; H2O2; metmyoglobin; proliferation