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果实提取物可保护环孢素A大鼠免受肝肾毒性并改变代谢离子。

fructus extract protects against hepatorenal toxicity and changes metabolic ions in cyclosporine A rats.

作者信息

Wei Yanyan, Luo Zhengzhong, Zhou Kang, Wu Quanwu, Xiao Wen, Yu Yang, Li Tongming

机构信息

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

出版信息

Nat Prod Res. 2021 Sep;35(17):2915-2920. doi: 10.1080/14786419.2019.1672688. Epub 2019 Oct 7.

Abstract

While cyclosporin A (CsA) is an effective immunosuppressive agent, its clinical application is limited by serious hepatorenal toxicity. However, fructus extract (SCE) has been previously shown to alleviate the hepatorenal damage caused by CsA. In this study, we aimed to evaluate the protective effects of SCE against hepatorenal toxicity induced by CsA. Our results revealed that SCE can prevent and treat CsA-induced liver and kidney injury. Furthermore, SCE inhibited the upward trend of dUDP and CDP-ethanolamine in the urine of CsA rats, pathways of which are involved in pyrimidine and glycerophospholipid metabolism. We finally confirmed that this protection of SCE was regulated by the activation of Nrf2 signaling pathway and the inhibition of apoptosis. In summary, our findings indicated that SCE may effectively prevent and treat hepatorenal toxicity caused by CsA. In addition, metabolomic techniques identified potential biomarkers for the occurrence of hepatorenal toxicity in CsA rats.

摘要

虽然环孢素A(CsA)是一种有效的免疫抑制剂,但其临床应用受到严重肝肾毒性的限制。然而,之前已证明五味子提取物(SCE)可减轻CsA引起的肝肾损伤。在本研究中,我们旨在评估SCE对CsA诱导的肝肾毒性的保护作用。我们的结果显示,SCE可预防和治疗CsA诱导的肝和肾损伤。此外,SCE抑制了CsA大鼠尿液中dUDP和CDP-乙醇胺的上升趋势,其途径参与嘧啶和甘油磷脂代谢。我们最终证实,SCE的这种保护作用是通过激活Nrf2信号通路和抑制细胞凋亡来调节的。总之,我们的研究结果表明,SCE可能有效预防和治疗CsA引起的肝肾毒性。此外,代谢组学技术鉴定出了CsA大鼠肝肾毒性发生的潜在生物标志物。

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