Ricardo S D, Bertram J F, Ryan G B
Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Vic., Australia.
Exp Nephrol. 1995 Sep-Oct;3(5):270-9.
The role of xanthine oxidase as a source of reactive oxygen species in puromycin aminonucleoside nephrosis was examined. The effects of allopurinol (a xanthine oxidase inhibitor as well as a reactive oxygen species scavenging enzyme) and tungsten (a specific xanthine oxidase inhibitor) on glomerular epithelial cell ultrastructure, renal xanthine oxidase and xanthine dehydrogenase activity, and urinary protein excretion were examined in puromycin aminonucleoside-treated rats. Co-administration of allopurinol to such rats reduced proteinuria by approximately 70% over the 10 days studied, and reduced the degree of glomerular epithelial cell foot process effacement at both 5 and 10 days, compared to rats that received puromycin aminonucleoside alone. Unexpectedly, co-administration of allopurinol to puromycin aminonucleoside-treated rats did not reduce xanthine oxidase activity; however, the combined activity of xanthine oxidase and xanthine dehydrogenase in such animals was reduced on day 5. Co-administration of tungsten to puromycin aminonucleoside-treated rats did not reduce proteinuria or alter the number of filtration slits. Rats co-administered tungsten and puromycin aminonucleoside had significantly reduced renal xanthine oxidase and combined xanthine oxidase and xanthine dehydrogenase activities on days 5 and 10, compared to rats treated with puromycin aminonucleoside alone. These results provide evidence that the protection provided by allopurinol in puromycin aminonucleoside-treated rats is due to the antioxidant properties of allopurinol, rather than to its activities as a xanthine oxidase inhibitor.
研究了黄嘌呤氧化酶作为嘌呤霉素氨基核苷肾病中活性氧来源的作用。在嘌呤霉素氨基核苷处理的大鼠中，检测了别嘌呤醇（一种黄嘌呤氧化酶抑制剂以及活性氧清除酶）和钨（一种特异性黄嘌呤氧化酶抑制剂）对肾小球上皮细胞超微结构、肾脏黄嘌呤氧化酶和黄嘌呤脱氢酶活性以及尿蛋白排泄的影响。与仅接受嘌呤霉素氨基核苷的大鼠相比，在研究的10天内，给此类大鼠联合使用别嘌呤醇可使蛋白尿减少约70%，并在第5天和第10天减轻肾小球上皮细胞足突消失的程度。出乎意料的是，给嘌呤霉素氨基核苷处理的大鼠联合使用别嘌呤醇并未降低黄嘌呤氧化酶活性；然而，此类动物中黄嘌呤氧化酶和黄嘌呤脱氢酶的联合活性在第5天有所降低。给嘌呤霉素氨基核苷处理的大鼠联合使用钨并未降低蛋白尿或改变滤过裂隙的数量。与仅用嘌呤霉素氨基核苷处理的大鼠相比，联合使用钨和嘌呤霉素氨基核苷的大鼠在第5天和第10天肾脏黄嘌呤氧化酶以及黄嘌呤氧化酶和黄嘌呤脱氢酶的联合活性显著降低。这些结果提供了证据，表明别嘌呤醇对嘌呤霉素氨基核苷处理的大鼠的保护作用是由于别嘌呤醇的抗氧化特性，而非其作为黄嘌呤氧化酶抑制剂的活性。
