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丙烯腈对Fischer-344大鼠的急性肾毒性潜力。

Acute nephrotoxic potential of acrylonitrile in Fischer-344 rats.

作者信息

Rouisse L, Chakrabarti S, Tuchweber B

出版信息

Res Commun Chem Pathol Pharmacol. 1986 Sep;53(3):347-60.

PMID:3775103
Abstract

In view of its very limited information, we have evaluated the acute nephrotoxic potential of acrylonitrile (ACN) in male Fischer-344 rats. ACN was given i.p. in saline to groups of 6 rats at doses 0, 10, 20, 40, 60 and 80 mg/kg. Urines were collected for 48 h and the animals were sacrificed at 24 and 48 h after the exposure. Significant increased levels of urinary volumes, glucose as well as increased levels of N-acetyl-beta-D-glucosaminidase (NAG), were observed at higher dose levels of ACN at 24 h. Light microscopy showed an increase in size and number of renal lysosomes or dense bodies at 60 mg ACN per kg after 48 h. Ultrastructural studies showed increase of dense bodies and endocytotic vacuoles at the same higher dose of ACN at 48 h. Autophagic vacuole formation as well as dilatation of endoplasmic reticulum membranes was also noted at the higher dose level. Acute inhalation exposure to ACN at 200 ppm for 4 h produced increases in the urinary volumes, proteins, glucose, gamma-GT and NAG 24 h after the exposure. These results demonstrate that ACN could produce acute nephrotoxic insult preferably at the proximal tubular region of the rat kidney.

摘要

鉴于其信息非常有限,我们评估了丙烯腈(ACN)对雄性Fischer-344大鼠的急性肾毒性潜力。将ACN溶于生理盐水中,以0、10、20、40、60和80mg/kg的剂量腹腔注射给每组6只大鼠。收集尿液48小时,并在暴露后24小时和48小时处死动物。在24小时时,在较高剂量的ACN组中观察到尿量、葡萄糖水平显著升高,以及N-乙酰-β-D-氨基葡萄糖苷酶(NAG)水平升高。光学显微镜显示,在48小时后,每千克60mg ACN剂量组的肾溶酶体或致密体的大小和数量增加。超微结构研究显示,在48小时时,相同较高剂量的ACN组中致密体和内吞空泡增加。在较高剂量水平还观察到自噬泡形成以及内质网膜扩张。急性吸入200ppm ACN 4小时后,在暴露后24小时尿量、蛋白质、葡萄糖、γ-谷氨酰转移酶(γ-GT)和NAG增加。这些结果表明,ACN可在大鼠肾脏近端小管区域产生急性肾毒性损伤。

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