Nukatsuka M, Yoshimura Y, Nishida M, Kawada J
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
J Pharmacobiodyn. 1990 Apr;13(4):259-62. doi: 10.1248/bpb1978.13.259.
Isolated rat pancreatic beta 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 dose-dependent inhibition of the decreased secretion of insulin by the cells induced by STZ (2 mM, for 1 h), 500 microM allopurinol causing complete inhibition of this effect of STZ. Pretreatment with allopurinol (250 microM) also prevented the rapid decrease in intracellular adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide concentrations in beta 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.
实验表明，单层培养的分离大鼠胰岛β细胞可被别嘌呤醇保护，免受链脲佐菌素（STZ）的细胞毒性作用。用别嘌呤醇预处理2小时可对STZ（2 mM，作用1小时）诱导的细胞胰岛素分泌减少产生剂量依赖性抑制，500 microM别嘌呤醇可完全抑制STZ的这种作用。用别嘌呤醇（250 microM）预处理还可防止STZ处理诱导的β细胞内三磷酸腺苷（ATP）和烟酰胺腺嘌呤二核苷酸浓度的快速下降。高效液相色谱显示，STZ处理细胞内尿酸浓度约为对照细胞的3倍。这一发现表明，暴露于STZ的细胞中黄嘌呤氧化酶反应可能因细胞内ATP减少导致底物供应增加而加速。基于这些结果，讨论了别嘌呤醇通过黄嘌呤氧化酶对STZ细胞毒性作用的可能机制。
