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铂类药物导致肾脏和肝脏中氨基酸的消耗。

Platinum-based drug-induced depletion of amino acids in the kidneys and liver.

作者信息

Mitrevska Katerina, Cernei Natalia, Michalkova Hana, Rodrigo Migue Angel Merlos, Sivak Ladislav, Heger Zbynek, Zitka Ondrej, Kopel Pavel, Adam Vojtech, Milosavljevic Vedran

机构信息

Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czechia.

Central European Institute of Technology, Brno University of Technology, Brno, Czechia.

出版信息

Front Oncol. 2022 Sep 21;12:986045. doi: 10.3389/fonc.2022.986045. eCollection 2022.

Abstract

Cisplatin (cis-diamminedichloroplatinum II; CDDP) is a widely used cytostatic agent; however, it tends to promote kidney and liver disease, which are a major signs of drug-induced toxicity. Platinum compounds are often presented as alternative therapeutics and subsequently easily dispersed in the environment as contaminants. Due to the major roles of the liver and kidneys in removing toxic materials from the human body, we performed a comparative study of the amino acid profiles in chicken liver and kidneys before and after the application of CDDP and platinum nanoparticles (PtNPs-10 and PtNPs-40). The treatment of the liver with the selected drugs affected different amino acids; however, Leu and Arg were decreased after all treatments. The treatment of the kidneys with CDDP mostly affected Val; PtNPs-10 decreased Val, Ile and Thr; and PtNPs-40 affected only Pro. In addition, we tested the same drugs on two healthy cell lines, HaCaT and HEK-293, and ultimately explored the amino acid profiles in relation to the tricarboxylic acid cycle (TCA) and methionine cycle, which revealed that in both cell lines, there was a general increase in amino acid concentrations associated with changes in the concentrations of the metabolites of these cycles.

摘要

顺铂(顺二氯二氨合铂II;CDDP)是一种广泛使用的细胞抑制剂;然而,它往往会引发肾脏和肝脏疾病,这是药物诱导毒性的主要迹象。铂化合物常被用作替代疗法,随后很容易作为污染物分散在环境中。由于肝脏和肾脏在清除人体有毒物质方面发挥着主要作用,我们对应用CDDP和铂纳米颗粒(PtNPs - 10和PtNPs - 40)前后鸡肝脏和肾脏中的氨基酸谱进行了比较研究。用所选药物处理肝脏会影响不同的氨基酸;然而,所有处理后亮氨酸(Leu)和精氨酸(Arg)均减少。用CDDP处理肾脏主要影响缬氨酸(Val);PtNPs - 10使Val、异亮氨酸(Ile)和苏氨酸(Thr)减少;而PtNPs - 40仅影响脯氨酸(Pro)。此外,我们在两种健康细胞系HaCaT和HEK - 293上测试了相同的药物,并最终探索了与三羧酸循环(TCA)和甲硫氨酸循环相关的氨基酸谱,结果表明在这两种细胞系中,与这些循环代谢物浓度变化相关的氨基酸浓度普遍增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403d/9535364/29ce5c0011e9/fonc-12-986045-g001.jpg

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