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用节段特异性肾毒物处理后通过尿排泄测定大鼠肾内谷氨酰胺转氨酶K的定位

Glutamine transaminase K intranephron localization in rats determined by urinary excretion after treatment with segment-specific nephrotoxicants.

作者信息

Trevisan A, Cristofori P, Fanelli G, Bicciato F, Stocco E

机构信息

Laboratory of Industrial Toxicology, Institute of Occupational Health, University of Padova, Italy.

出版信息

Arch Toxicol. 1998 Jul-Aug;72(8):531-5. doi: 10.1007/s002040050538.

Abstract

Glutamine transaminase K(GTK) excretion assessed in urine and by kidney histology was evaluated in rats after single treatment with 1.0 mg/kg i.p. of mercuric chloride, 100 mg/kg i.p. of hexachloro-1:3-butadiene (both S3, pars recta, segment-specific nephrotoxicants) and 25 mg/kg s.c. of potassium dichromate (S1-S2, pars convoluta, segment-specific nephrotoxicant). The aim was to correlate segment-specific injury and enzyme excretion in order to assess, using non-vasive methods, localization of GTK along the proximal tubule. Mercuric chloride and hexachloro-1:3-butadiene produced early focal damage in the pars recta (focal necrosis was shown 10 h after treatment, and diffuse necrosis appeared later at 34 and 24 h after treatment). Changes of the pars convoluta were occasional and delayed (72 h after treatment for both substances). On the contrary, potassium dichromate induced damage of the pars convoluta (vacuolar degeneration and focal necrosis were evident 24 h and 48 h after treatment, respectively), whereas the pars recta was affected later (focal vacuolar degeneration was observed 72 h after treatment). Increase urinary GTK excretion was early after treatment with mercuric chloride and hexachloro-1:3-butadiene (significant increase was observed within 10 h), with a peak for both substances 24 h after treatment, in agreement with the necrosis of the pars recta. Potassium dichromate induced a significant increase of enzyme excretion in urine also 24 h after injection, according to histological features showing vacuolar degeneration of the pars convoluta; the peak of excretion was reached 48 h after treatment (delay was due, probably, to s.c. administration). The results show that GTK increased in urine after treatment with S3 and S1-S2 specific nephrotoxicants; the combination of histological examination and urinary enzyme supports the evidence that the enzyme is distributed along the whole of the proximal tubule.

摘要

在用1.0毫克/千克腹腔注射氯化汞、100毫克/千克腹腔注射六氯-1:3-丁二烯(两者均为S3,直部,节段特异性肾毒物)和25毫克/千克皮下注射重铬酸钾(S1 - S2,曲部,节段特异性肾毒物)单次处理大鼠后,对尿中谷氨酰胺转氨酶K(GTK)排泄及通过肾脏组织学进行了评估。目的是关联节段特异性损伤与酶排泄,以便使用非侵入性方法评估GTK沿近端小管的定位。氯化汞和六氯-1:3-丁二烯在直部产生早期局灶性损伤(处理后10小时显示局灶性坏死,随后在处理后34小时和24小时出现弥漫性坏死)。曲部的变化偶尔出现且延迟(两种物质处理后72小时)。相反,重铬酸钾诱导曲部损伤(处理后24小时和48小时分别出现空泡变性和局灶性坏死),而直部稍后受到影响(处理后72小时观察到局灶性空泡变性)。用氯化汞和六氯-1:3-丁二烯处理后,尿中GTK排泄早期增加(处理后10小时内观察到显著增加),两种物质在处理后24小时达到峰值,这与直部坏死一致。根据显示曲部空泡变性的组织学特征,重铬酸钾在注射后24小时也导致尿中酶排泄显著增加;排泄峰值在处理后48小时达到(延迟可能是由于皮下给药)。结果表明,用S3和S1 - S2特异性肾毒物处理后尿中GTK增加;组织学检查和尿酶的结合支持了该酶沿整个近端小管分布的证据。

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