Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Alpha-Lipoic Acid Treatment Reverses 2-Deoxy-D-ribose-Induced Oxidative Damage and Suppression of Insulin Expression in Pancreatic Beta-Cells
Gwanpyo KohEun-Jin YangMin-Kyoung KimSang Ah LeeDae-Ho Lee
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2013 Volume 36 Issue 10 Pages 1570-1576

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Abstract

We investigated whether α-lipoic acid (LA) could prevent 2-deoxy-D-ribose (dRib)-induced oxidative damage and suppression of insulin expression in pancreatic β-cells. Stimulation with 50 mM dRib elevated cytotoxicity, apoptosis and intracellular reactive oxygen species (ROS) levels in HIT-T15 cells, but pretreatment with LA significantly reversed the dRib-induced changes. LA directly scavenged hydroxyl radicals generated by a Fenton reaction. Intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) were depleted by stimulation with dRib but levels were restored by addition of LA to HIT-T15 cells. However, the GSH/GSSG ratio was unchanged by LA treatment. In rat islets, stimulation with 10 mM dRib for 6 h suppressed expression of insulin and pancreatic and duodenal homeobox 1 mRNA and decreased insulin content, but these were dose-dependently reversed when LA was added. Treatment with l-buthionine-sulfoximine, an inhibitor of intracellular glutathione biosynthesis, completely abolished the protective effects of LA on dRib-mediated glutathione depletion and cytotoxicity in HIT-T15 cells. In summary, LA reversed the dRib-induced oxidative damage and suppression of insulin expression in β-cells. Enhanced intracellular total glutathione production, rather than the scavenging of ROS, is possibly the mechanism for the protective effect of LA.

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© 2013 The Pharmaceutical Society of Japan
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