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摇头丸所致肾毒性后的时间依赖性分子变化

Time-Dependent Molecular Changes Following MDMA-Induced Nephrotoxicity.

作者信息

Roghani Mehrdad, Golchoobian Ravieh, Mohammadian Maryam, Shanehbandpour-Tabari Farzane, Salehi Zahra, Gilaki-Bisheh Saba

机构信息

Neurophysiology Research Center, Shahed University, Tehran, Iran.

Department of Physiology, Babol University of Medical Sciences, Babol, Iran.

出版信息

Iran J Pharm Res. 2024 May 18;23(1):e145483. doi: 10.5812/ijpr-145483. eCollection 2024 Jan-Dec.

Abstract

The increasing recreational use of ecstasy (MDMA) poses significant risks to human health, including reports of fatal renal failure due to its adverse renal effects. While MDMA-induced renal toxicity might result from systemic effects, there is also substantial evidence of direct harm to renal tissues by MDMA or its metabolites. The precise mechanisms underlying renal toxicity remain unclear. This study explored the impact of a single intraperitoneal dose of MDMA (20 mg/kg) on rat kidneys. Serum BUN and creatinine levels were evaluated to assess renal function, while TNF-α and TGF-β protein concentrations were measured using ELISA. mRNA levels of Bax, Bcl-xl, and Bcl-2 were quantified using quantitative RT-PCR. Additionally, apoptosis and histopathological changes in renal tissue were examined. Results showed a transient increase in serum BUN and creatinine in MDMA-treated rats. There were decreases in TNF-α and TGF-β levels in the renal tissue. Both pro-apoptotic Bax and anti-apoptotic Bcl-xl gene expressions were significantly reduced, whereas Bcl-2 expression and apoptosis did not show significant changes. No structural alterations were observed in the renal tissues. Overall, this study suggests that the renal adverse effects of MDMA may be mediated through the disruption of cytokine pathways, with notable reductions in TGF-β possibly linked to decreased TNF-α levels.

摘要

摇头丸(3,4-亚甲基二氧甲基苯丙胺,MDMA)在娱乐场合的使用日益增加,对人类健康构成了重大风险,其中包括因MDMA对肾脏的不良影响导致致命肾衰竭的报告。虽然MDMA诱发的肾毒性可能源于全身效应,但也有大量证据表明MDMA或其代谢产物会对肾组织造成直接损害。肾毒性的确切机制尚不清楚。本研究探讨了腹腔注射单次剂量MDMA(20毫克/千克)对大鼠肾脏的影响。通过评估血清尿素氮(BUN)和肌酐水平来评估肾功能,同时使用酶联免疫吸附测定(ELISA)法检测肿瘤坏死因子-α(TNF-α)和转化生长因子-β(TGF-β)的蛋白浓度。使用定量逆转录-聚合酶链反应(RT-PCR)对Bax、Bcl-xl和Bcl-2的mRNA水平进行定量分析。此外,还检查了肾组织中的细胞凋亡情况和组织病理学变化。结果显示,接受MDMA治疗的大鼠血清BUN和肌酐出现短暂升高。肾组织中TNF-α和TGF-β水平降低。促凋亡基因Bax和抗凋亡基因Bcl-xl的表达均显著降低,而Bcl-2的表达和细胞凋亡未显示出显著变化。肾组织未观察到结构改变。总体而言,本研究表明,MDMA对肾脏的不良影响可能是通过细胞因子途径的破坏介导的,TGF-β的显著降低可能与TNF-α水平降低有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04c6/11742579/06c54714e169/ijpr-23-1-145483-i001.jpg

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