Allopurinol Protects Pancreatic β Cells from the Cytotoxic Effect of Streptozotocin : In Vitro Study

概要

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Isolated rat pancreatic β cells in monolayer culture were shown to be protected from the cytotoxic effect of streptozotocin (STZ) by allopurinol. Pretreatment with allopurinol for 2 h caused dosedependent inhibition of the decreased secretion of insulin by the cells induced by STZ (2 mM, for 1 h), 500μM allopurinol causing complete inhibition of this effect of STZ. Pretreatment with allopurinol (250μM) also prevented the rapid decrease in intracellular adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide concentrations in β cells induced by treatment with STZ. High performance liquid chromatography revealed that the intracellular concentration of uric acid in STZ-treated cells was about 3 fold that of control cells. This finding suggests that the reaction of xanthine oxidase is facilitated in the cells exposed to STZ probably due to an increased supply of substrate resulting from decrease in intracellular ATP. Based on these results, a possible mechanism of the effect of allopurinol on the cytotoxic effect of STZ via xanthine oxidase is discussed.
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