Annals of the New York Academy of Sciences · 2005 · 99 citations · 16 references
Life SciencesCell BiologyPharmacologyApoptosisCellular MetabolismInflammationApoptosis PharmacologyHepatotoxicity MechanismsOxidative Stress In HepatotoxicityReactive Oxygen SpeciesApoptosis In HepatotoxicityApoptotic Morphological ChangesDiabetic ComplicationsOxidative Stress In DiabetesOxidative Stress-induced ApoptosisReactive Oxygen Species GenerationReactive Oxygen Species InjuryReactive Oxygen Species-induced Apoptosis
Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Elevated MG levels in diabetes patients are believed to contribute to diabetic complications. MG is cytotoxic through induction of apoptosis. Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties. In the present study, we investigated the effect of curcumin on MG-induced apoptotic events in human hepatoma G2 cells. We report that curcumin prevented MG-induced cell death and apoptotic biochemical changes such as mitochondrial release of cytochrome c, caspase-3 activation, and cleavage of PARP (poly [ADP-ribose] polymerase). Using the cell permeable dye 2',7'-dichlorofluorescein diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation, we found that curcumin abolished MG-stimulated intracellular oxidative stress. The results demonstrate that curcumin significantly attenuates MG-induced ROS formation, and suggest that ROS triggers cytochrome c release, caspase activation, and subsequent apoptotic biochemical changes.
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