Oxidative stress has been proposed as a mechanism of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The aim of this research was to evaluate the protective effects of increased intracellular ascorbate levels against TCDD acute toxicity in the insulin-secreting beta-cell line INS-1E. Ascorbate is considered a potent antioxidant,but its therapeutic efficacy is greatly limited by its slow achievement of high intracellular levels. This might be circumvented by administration of dehydroascorbate (DNA), which is transported at a much higher rate and undergoes rapid intracellular reduction to ascorbate. Indeed, 30 min incubation of INS-1E cells with various concentrations of DHA caused a remarkable, dose-related increase of the intracellular ascorbate levels. INS-1E cells preincubated with 0.5 and 1.0 mM DHA showed a greater viability than control cells after 1 h exposition to cytotoxic TCDD concentrations. In our experimental conditions, TCDD surprisingly failed to increase ROS production in INS-1E cells, but induced a dose-related mitochondrial depolarisation which was significantly improved by DHA preincubation. Furthermore, DHA preincubation completely prevented the low dose TCDD-induced inhibition of glucose-stimulated insulin secretion. Thus, our results suggest that DHA preincubation protects INS-1E cells against TCDD acute toxicity by partially preserving mitochondrial function. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
Dehydroascorbate protection against dioxin-induced toxicity in the beta-cell line INS-1E
MARTINO, LUISA;NOVELLI, MICHELA;MASINI, MATILDE;PIAGGI, SIMONA;MASIELLO, PELLEGRINO;DE TATA, VINCENZO
2009-01-01
Abstract
Oxidative stress has been proposed as a mechanism of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The aim of this research was to evaluate the protective effects of increased intracellular ascorbate levels against TCDD acute toxicity in the insulin-secreting beta-cell line INS-1E. Ascorbate is considered a potent antioxidant,but its therapeutic efficacy is greatly limited by its slow achievement of high intracellular levels. This might be circumvented by administration of dehydroascorbate (DNA), which is transported at a much higher rate and undergoes rapid intracellular reduction to ascorbate. Indeed, 30 min incubation of INS-1E cells with various concentrations of DHA caused a remarkable, dose-related increase of the intracellular ascorbate levels. INS-1E cells preincubated with 0.5 and 1.0 mM DHA showed a greater viability than control cells after 1 h exposition to cytotoxic TCDD concentrations. In our experimental conditions, TCDD surprisingly failed to increase ROS production in INS-1E cells, but induced a dose-related mitochondrial depolarisation which was significantly improved by DHA preincubation. Furthermore, DHA preincubation completely prevented the low dose TCDD-induced inhibition of glucose-stimulated insulin secretion. Thus, our results suggest that DHA preincubation protects INS-1E cells against TCDD acute toxicity by partially preserving mitochondrial function. (C) 2009 Elsevier Ireland Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
