Antioxidant and prooxidant effects of phenolics on pancreatic beta-cells in vitro.
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 beta-cells have been reported to exhibit particular sensitivity to oxidative stress, a factor that may contribute to the impaired beta-cell function characteristic of diabetes. The aim of this study was to examine the potential of natural phenolics to protect cultured pancreatic beta-cells (betaTC1 and HIT) from H(2)O(2) oxidative stress. Exposure of cells to H(2)O(2) led to significant proliferation inhibition. Contrary to what one should expect, simultaneous exposure to H(2)O(2) and the phenolics, quercetin (10-100 microM), catechin (50-500 microM), or ascorbic acid (100-1000 microM), led to amplification of proliferation inhibition. At higher concentrations, these compounds inhibited proliferation, even in the absence of added H(2)O(2). This prooxidant effect is attributable to the generation of H(2)O(2) through interaction of the added phenolic compounds with as yet undefined componenets of the culture media. On the other hand, inclusion of metmyoglobin (30 microM) 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 microM, each) prior to application of oxidative stress. It is concluded that provided artifactual prooxidant effects are avoided, preincubation of beta-cells with relatively hydrophobic natural phenolics can confer protection against oxidative stress.
Lapidot
Tair
T
Department of Food Science, ARO Volcani Center, Bet Dagan 50250, Israel.
Walker
Michael D
MD
Kanner
Joseph
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology; D002392:Catechin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005419:Flavonoids / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008786:Metmyoglobin / Q000494:pharmacology; D051379:Mice; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology
D000975:Antioxidants; D002109:Caffeic Acids; D005419:Flavonoids; D016877:Oxidants; D010636:Phenols; D008786:Metmyoglobin; C043561:chrysin; D002392:Catechin; D011794:Quercetin; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; C040048:caffeic acid