Suppr超能文献

肾毒性化合物二甘醇的神经毒性作用。

Neurotoxic effects of nephrotoxic compound diethylene glycol.

机构信息

Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center, Shreveport, LA, USA.

出版信息

Clin Toxicol (Phila). 2021 Sep;59(9):810-821. doi: 10.1080/15563650.2021.1874403. Epub 2021 Jan 21.

Abstract

CONTEXT

Diethylene glycol (DEG) is an organic compound found in household products but also as an adulterant in medicines by acting as a counterfeit solvent. DEG poisonings have been characterized predominately by acute kidney injury (AKI), but also by delayed neurological sequelae such as decreased reflexes or face and limb weakness.

OBJECTIVES

Characterizing the neurological symptoms of DEG poisoning in a subacute animal model would create a clearer picture of overall toxicity and possibly make mechanistic connections between kidney injury and neuropathy.

METHODS

Male Wistar-Han rats were orally administered doses of 4 - 6 g/kg DEG every 12 or 24 h and monitored for 7 days. Urine was collected every 12 h and endpoint blood and cerebrospinal fluid (CSF) were collected for a renal plasma panel and total protein estimation, respectively. Motor function tests were conducted before and after treatment. Kidney and brain tissue was harvested for metabolic analysis.

RESULTS

Of the 43 animals treated with DEG, 11 developed AKI as confirmed by increased BUN and creatinine levels. Renal and brain DGA accumulation was markedly increased in animals that developed AKI compared to animals without AKI. The total protein content in CSF in animals with kidney injury was markedly elevated compared to control and to treated animals without AKI. Significant decreases in forelimb grip strength and decreases in locomotor and rearing activity were observed in animals with AKI compared to control and to animals without AKI.

DISCUSSION

Repeated dosing with DEG in an animal model produced nephrotoxic effects like those in studies with acute DEG administration. The decrease in motor function and increase in CSF protein were only present in animals that developed AKI.

CONCLUSIONS

These studies show development of neurotoxicity in this DEG animal model and suggest that neurological symptoms are observed only when DGA accumulation and kidney injury also occur.

摘要

背景

二甘醇(DEG)是一种存在于家用产品中的有机化合物,但也可作为药物中的掺杂物,充当假冒溶剂。DEG 中毒主要表现为急性肾损伤(AKI),但也有延迟性神经后遗症,如反射减弱或面部和肢体无力。

目的

在亚急性动物模型中描述 DEG 中毒的神经症状,将更清楚地了解其整体毒性,并可能在肾损伤和神经病变之间建立机制联系。

方法

雄性 Wistar-Han 大鼠口服 4-6g/kg DEG 剂量,每 12 或 24 小时一次,并监测 7 天。每隔 12 小时收集尿液,在治疗前后进行运动功能测试,并分别采集终点血液和脑脊液(CSF)进行肾脏血浆分析和总蛋白估计。采集肾脏和脑组织进行代谢分析。

结果

在接受 DEG 治疗的 43 只动物中,有 11 只动物出现 AKI,表现为 BUN 和肌酐水平升高。与未发生 AKI 的动物相比,发生 AKI 的动物的肾脏和大脑 DGA 积累明显增加。与对照动物和无 AKI 的治疗动物相比,有肾脏损伤的动物 CSF 中的总蛋白含量明显升高。与对照动物和无 AKI 的治疗动物相比,发生 AKI 的动物的前肢握力明显下降,运动和站立活动减少。

讨论

在动物模型中重复给予 DEG 会产生类似急性 DEG 给药研究中的肾毒性作用。只有在发生 AKI 的动物中才观察到运动功能下降和 CSF 蛋白增加。

结论

这些研究表明,在该 DEG 动物模型中出现了神经毒性,表明仅在 DGA 积累和肾脏损伤发生时才观察到神经症状。

相似文献

1
Neurotoxic effects of nephrotoxic compound diethylene glycol.肾毒性化合物二甘醇的神经毒性作用。
Clin Toxicol (Phila). 2021 Sep;59(9):810-821. doi: 10.1080/15563650.2021.1874403. Epub 2021 Jan 21.
2
Diethylene glycol produces nephrotoxic and neurotoxic effects in female rats.二甘醇会对雌性大鼠产生肾毒性和神经毒性。
Clin Toxicol (Phila). 2022 Mar;60(3):324-331. doi: 10.1080/15563650.2021.1953049. Epub 2021 Jul 19.

本文引用的文献

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验