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丙亚胺的肾毒性:大鼠无创技术评估

Renal toxicity of propyleneimine: assessment by non-invasive techniques in the rat.

作者信息

Halman J, Miller J, Fowler J S, Price R G

出版信息

Toxicology. 1986 Oct;41(1):43-59. doi: 10.1016/0300-483x(86)90103-4.

Abstract

The nephrotoxicity of three different dose levels of propyleneimine (10, 20 and 30 microliter/kg body wt) administered intraperitoneally to rats was studied and 20 microliters/kg body weight was found to be the most appropriate sublethal dose. Injection of propyleneimine (10 microliters/kg body wt) produced a small rise in N-acetyl-beta-D-glucosaminidase (NAG) activity, minor histological damage but no change in urine volume. Six rats were injected with 20 microliters/kg body weight, and urine was collected over the following 16 days. An immediate increase in urine volume, osmolality together with a concomitant decrease in specific gravity, was accompanied by a small increase in creatinine excretion and a more marked increase in the sodium and potassium content of urine after the administration of the nephrotoxin. NAG activity increased immediately and peaked on day 3, the activity remained elevated until day 12 when it fell to near normal levels. The activity of both beta-D-galactosidase and beta-D-glucosidase increased 9 days after administration of the nephrotoxin. In contrast, no consistent change was found in the excretion of the brush border marker enzymes, leucine aminopeptidase (LAP), alanine aminopeptidase (AAP) or alkaline phosphatase (ALP). Proteinuria increased sharply the day after injection and remained abnormal. Increased urinary albumin excretion and the predominance of low molecular weight proteins was demonstrated by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. Evidence is presented that propyleneimine exerts its early toxic effect on the renal papilla.

摘要

研究了腹腔注射三种不同剂量水平的丙撑亚胺(10、20和30微升/千克体重)对大鼠的肾毒性,发现20微升/千克体重是最合适的亚致死剂量。注射丙撑亚胺(10微升/千克体重)使N - 乙酰 - β - D - 氨基葡萄糖苷酶(NAG)活性略有升高,造成轻微的组织学损伤,但尿量无变化。给6只大鼠注射20微升/千克体重,并在接下来的16天收集尿液。注射肾毒素后,尿量立即增加,尿渗透压随之增加,同时比重降低,肌酐排泄量略有增加,尿钠和钾含量增加更为明显。NAG活性立即升高,并在第3天达到峰值,该活性一直保持升高直到第12天,此时降至接近正常水平。在注射肾毒素9天后,β - D - 半乳糖苷酶和β - D - 葡萄糖苷酶的活性均增加。相比之下,刷状缘标记酶亮氨酸氨肽酶(LAP)、丙氨酸氨肽酶(AAP)或碱性磷酸酶(ALP)的排泄没有一致的变化。注射后第二天蛋白尿急剧增加且仍异常。十二烷基硫酸钠(SDS)聚丙烯酰胺凝胶电泳显示尿白蛋白排泄增加且低分子量蛋白质占优势。有证据表明丙撑亚胺对肾乳头产生早期毒性作用。

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