Lee Dahae, Hyuk Lee Sang, Lee Heesu, Choi You-Kyung, Sung Kang Ki, Wook Lee Jae
College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea.
Natural Product Research Center, Korea Institute of Science and Technology, Saimdang-ro 679, Gangneung 25451, Republic of Korea.
Bioorg Med Chem Lett. 2023 Jan 15;80:129114. doi: 10.1016/j.bmcl.2022.129114. Epub 2022 Dec 24.
This study aimed to explore the renoprotective effects of oxime derivatives against cisplatin-mediated cell death in LLC-PK1 porcine kidney epithelial cells. Treatment with compounds 161-A and 161-F improved cisplatin-mediated LLC-PK1 cell damage and increased cell viability by more than 80% of the control value when compared with that of cisplatin-treated cells. In addition, 161-A and 161-F reduced cisplatin-induced apoptosis. Analysis of the molecular mechanisms underlying the effects exerted by these compounds revealed that treatment with 161-A and 161-B inhibited the protein expression of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) and cleaved caspase-3 in cisplatin-treated LLC-PK1 cells. Thus, these findings provide in vitro scientific evidence that oxime derivatives may be useful as pharmacological candidates for the prevention of cisplatin-mediated nephrotoxicity.
本研究旨在探讨肟衍生物对顺铂介导的LLC-PK1猪肾上皮细胞死亡的肾保护作用。与顺铂处理的细胞相比,用化合物161-A和161-F处理可改善顺铂介导的LLC-PK1细胞损伤,并使细胞活力增加至对照值的80%以上。此外,161-A和161-F可减少顺铂诱导的细胞凋亡。对这些化合物作用的分子机制分析表明,用161-A和161-B处理可抑制顺铂处理的LLC-PK1细胞中细胞外信号调节激酶(ERK)和c-Jun氨基末端激酶(JNK)的蛋白表达以及半胱天冬酶-3的裂解。因此,这些发现提供了体外科学证据,表明肟衍生物可能作为预防顺铂介导的肾毒性的药理学候选物。