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单次给予腺嘌呤所致的肾毒性:4-氨基吡唑并[3,4-d]嘧啶和别嘌醇的作用

Nephrotoxicity induced by a single dose of adenine: effects of 4-aminopyrazolo[3,4-d]pyrimidine and allopurinol.

作者信息

Minami T, Nakagawa H, Ichii M, Kadota E, Okazaki Y

机构信息

Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.

出版信息

Biol Pharm Bull. 1994 Feb;17(2):201-6. doi: 10.1248/bpb.17.201.

DOI:10.1248/bpb.17.201
PMID:8205116
Abstract

The effects of allopurinol and 4-aminopyrazolo[3,4-d]pyrimidine (4APP) on adenine-induced renal injury in mice were examined. Plasma urea nitrogen (UN) and creatinine levels increased after the oral administration of adenine to mice. However, plasma UN and creatinine levels decreased inversely with the dose of 4APP when a different dosage of 4APP was administered together with adenine. Yet 4APP did not have any effect on the UN or creatinine levels when 4APP was administered after adenine administration. Plasma UN and creatinine levels increased in the allopurinol-administered group as in the adenine-administered group. Moreover, from light microscopic observation by hematoxylin-eosin staining, microvacuolic changes in the proximal tubuli were detected in the mouse kidney in the adenine-administered group, and epithelial cell loss, degeneration and microvacuolic changes in the proximal tubuli were observed in the mouse kidney in the adenine-and-allopurinol-administered group. However, there were no changes in the proximal tubuli in the mouse kidney in the adenine-and-4APP-administered group. These findings suggested that 4APP inhibits the action of adenine in the mouse kidney.

摘要

研究了别嘌呤醇和4-氨基吡唑并[3,4-d]嘧啶(4APP)对腺嘌呤诱导的小鼠肾损伤的影响。给小鼠口服腺嘌呤后,血浆尿素氮(UN)和肌酐水平升高。然而,当将不同剂量的4APP与腺嘌呤一起给药时,血浆UN和肌酐水平与4APP剂量呈反比下降。然而,在腺嘌呤给药后给予4APP时,4APP对UN或肌酐水平没有任何影响。与腺嘌呤给药组一样,别嘌呤醇给药组的血浆UN和肌酐水平升高。此外,通过苏木精-伊红染色进行光镜观察,在腺嘌呤给药组的小鼠肾脏中检测到近端小管的微泡样改变,在腺嘌呤和别嘌呤醇给药组的小鼠肾脏中观察到近端小管的上皮细胞丢失、变性和微泡样改变。然而,在腺嘌呤和4APP给药组的小鼠肾脏中,近端小管没有变化。这些发现表明,4APP抑制腺嘌呤在小鼠肾脏中的作用。

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引用本文的文献

1
4-Aminopyrazolo[3,4-d]pyrimidine (4-APP) as a novel inhibitor of the RNA and DNA depurination induced by Shiga toxin 1.4-氨基吡唑并[3,4-d]嘧啶(4-APP)作为一种新型抑制剂,可抑制志贺毒素1诱导的RNA和DNA脱嘌呤作用。
Nucleic Acids Res. 2000 Jun 15;28(12):2383-8. doi: 10.1093/nar/28.12.2383.