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六氯-1:3-丁二烯对大鼠肾脏的急性毒性作用。

The acute toxic effects of hexachloro-1 : 3-butadiene on the rat kidney.

作者信息

Lock E A, Ishmael J

出版信息

Arch Toxicol. 1979 Oct;43(1):47-57. doi: 10.1007/BF00695873.

Abstract

A single intraperitoneal injection of hexochloro-1 : 3-butadiene (HCBD) at 100 mg/kg or above produced renal tubular necrosis in the rat by 24 h. Histological examination of the kidneys indicated damage to the straight portion of the proximal tubules. Urinary analysis showed diuresis, increased proteinuria and an increase in the excretion of N-acetyl-beta-D-glucosaminidase, and alkaline phosphatase at doses above 100 mg/kg. At doses below 100 mg/kg only a mild increase in protein excretion was observed. Twenty-four hours after 200 mg/kg HCBD, i.p., there was a marked decrease in the glomerular filtration rate (inulin clearance) and in the clearance of the organic anion (p-aminohippuric acid, PAH) and the organic cation (tetraethylammonium bromide, TEA) by the kidney. HCBD did not affect the accumulation of PAH or TEA by renal cortical slices when added in vitro at a concentration up to 0.1 mM. However, a decrease in PAH, but not TEA accumulation, was seen in renal cortical slices from rats treated with HCBD 24 h previously. Mercuric chloride (HgCl2), a known nephrotoxin, was used as a positive control for these studies. HCBD appears to specifically damage the straight portion of the proximal renal tubule and thereby selectively damage the organic anion transport system.

摘要

以100mg/kg或更高剂量对大鼠进行腹腔内单次注射六氯-1:3-丁二烯(HCBD),24小时后会导致肾小管坏死。肾脏组织学检查表明近端小管直部受损。尿液分析显示,剂量高于100mg/kg时会出现利尿、蛋白尿增加以及N-乙酰-β-D-氨基葡萄糖苷酶和碱性磷酸酶排泄增加。剂量低于100mg/kg时,仅观察到蛋白质排泄轻度增加。腹腔注射200mg/kg HCBD 24小时后,肾小球滤过率(菊粉清除率)以及肾脏对有机阴离子(对氨基马尿酸,PAH)和有机阳离子(溴化四乙铵,TEA)的清除率显著降低。当体外添加浓度高达0.1mM的HCBD时,其不会影响肾皮质切片对PAH或TEA的摄取。然而,在24小时前用HCBD处理过的大鼠的肾皮质切片中,观察到PAH摄取减少,但TEA摄取未减少。已知的肾毒素氯化汞(HgCl2)用作这些研究的阳性对照。HCBD似乎特异性地损伤近端肾小管直部,从而选择性地损害有机阴离子转运系统。

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