大鼠肾毒性的肾小管节段特异性生物标志物。

Tubular segment-specific biomarkers of nephrotoxicity in the rat.

作者信息

Trevisan A, Giraldo M, Borella M, Bottegal S, Fabrello A

机构信息

Laboratory of Industrial Toxicology, Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, I-35128 Padova, Italy.

出版信息

Toxicol Lett. 2001 Oct 15;124(1-3):113-20. doi: 10.1016/s0378-4274(00)00282-4.

DOI:10.1016/s0378-4274(00)00282-4

PMID:11684363

Abstract

Segment-specific localization of p-aminohippuric acid accumulation and glutamine synthetase activity along the proximal tubule was investigated in kidneys of rats treated with segment-specific nephrotoxicants such as potassium dichromate (pars convoluta) and hexachloro-1:3-butadiene (pars recta). Potassium dichromate and the highest dose (200 mg/kg b.w.) of hexachloro-1:3-butadiene caused a significant, dose-dependent decrease of p-aminohippuric acid uptake in the renal cortical slices 24 and 48 h after the treatment. In contrast, hexachloro-1:3-butadiene and only the highest dose (40 mg/kg b.w.) of potassium dichromate, caused a significant dose-dependent decrease of glutamine synthetase activity in the kidney beginning 24 h after treatment. Finally, potassium dichromate and the highest dose (200 mg/kg b.w.) of hexachloro-1:3-butadiene (48 h after the treatment) caused a significant dose-dependent loss of kidney protein content. The results suggest that p-aminohippuric acid accumulation is localized in the pars convoluta and confirm that glutamine synthetase is in the pars recta of the rat proximal tubule. p-Aminohippuric acid uptake impairment and glutamine synthetase activity loss caused by the highest doses of hexachloro-1:3-butadiene and potassium dichromate, respectively, suggests that high doses of segment-specific chemicals may involve other portions of the proximal tubule; in addition, the decrease of glutamine synthetase activity caused by potassium dichromate may be related to the protein content loss.

摘要

在使用诸如重铬酸钾（曲部）和六氯 -1:3-丁二烯（直部）等节段特异性肾毒物处理的大鼠肾脏中，研究了对氨基马尿酸积累和谷氨酰胺合成酶活性沿近端小管的节段特异性定位。重铬酸钾和最高剂量（200 mg/kg体重）的六氯 -1:3-丁二烯在处理后24和48小时导致肾皮质切片中对氨基马尿酸摄取量显著的剂量依赖性降低。相比之下，六氯 -1:3-丁二烯以及仅最高剂量（40 mg/kg体重）的重铬酸钾在处理后24小时开始导致肾脏中谷氨酰胺合成酶活性显著的剂量依赖性降低。最后，重铬酸钾和最高剂量（200 mg/kg体重）的六氯 -1:3-丁二烯（处理后48小时）导致肾脏蛋白质含量显著的剂量依赖性损失。结果表明对氨基马尿酸积累定位于曲部，并证实谷氨酰胺合成酶位于大鼠近端小管的直部。分别由最高剂量的六氯 -1:3-丁二烯和重铬酸钾引起的对氨基马尿酸摄取受损和谷氨酰胺合成酶活性丧失表明，高剂量的节段特异性化学物质可能涉及近端小管的其他部分；此外，重铬酸钾引起的谷氨酰胺合成酶活性降低可能与蛋白质含量损失有关。