Bunel Valérian, Antoine Marie-Hélène, Nortier Joëlle, Duez Pierre, Stévigny Caroline
Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Laboratory of Pharmacognosy, Bromatology and Human Nutrition, Faculty of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium.
J Appl Toxicol. 2014 Dec;34(12):1311-9. doi: 10.1002/jat.2951. Epub 2013 Oct 24.
Renal proximal tubular epithelial cells are the main targets of toxic drugs such as cisplatin (CisPt), an alkylating agent indicated for the treatment of solid organ tumors. Current techniques aiming at reducing nephrotoxicity in patients receiving CisPt are still not satisfactory as they can only partially prevent acute kidney injury. New nephroprotective strategies remain to be developed. In the present in vitro study, schizandrin (Schi) and schizandrin B (Schi B), major phytochemicals from Schisandra chinensis (Turcz.) Baill. fruits, were tested on HK-2 cells along four processes that could help alleviate CisPt toxicity. Results indicated that: (i) both Schi and Schi B enhanced cell survival via reducing apoptosis rate; (ii) only Schi showed moderate effects towards modulation of regeneration capacities of healthy cells; (iii) both Schi and Schi B limited extracellular matrix deposition; and (iv) both compounds could help preventing dedifferentiation processes via the β-catenin pathway. Schi and Schi B present promising activities for future development of protective agents against CisPt nephrotoxicity.
肾近端小管上皮细胞是顺铂（CisPt）等毒性药物的主要作用靶点，顺铂是一种用于治疗实体器官肿瘤的烷化剂。目前旨在降低接受顺铂治疗患者肾毒性的技术仍不尽人意，因为它们只能部分预防急性肾损伤。新的肾保护策略仍有待开发。在本体外研究中，对来自五味子果实的主要植物化学成分五味子醇甲（Schi）和五味子醇乙（Schi B）进行了测试，它们作用于HK-2细胞的四个过程，这可能有助于减轻顺铂毒性。结果表明：（i）五味子醇甲和五味子醇乙均通过降低凋亡率提高细胞存活率；（ii）只有五味子醇甲对调节健康细胞的再生能力有中等作用；（iii）五味子醇甲和五味子醇乙均限制细胞外基质沉积；（iv）这两种化合物均可通过β-连环蛋白途径帮助预防去分化过程。五味子醇甲和五味子醇乙在未来开发抗顺铂肾毒性保护剂方面具有广阔的应用前景。
