Sinaeve Sébastien, Husson Cécile, Antoine Marie-Hélène, Welti Stéphane, Stévigny Caroline, Nortier Joëlle
RD3-Pharmacognosy, Bioanalysis and Drug Discovery Unit, Faculty of Pharmacy, Université Libre de Bruxelles, 1050 Brussels, Belgium.
Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, 1050 Brussels, Belgium.
J Fungi (Basel). 2022 Sep 24;8(10):1002. doi: 10.3390/jof8101002.
Although cisplatin is used as a first-line therapy in many cancers, its nephrotoxicity remains a real problem. Acute kidney injuries induced by cisplatin can cause proximal tubular necrosis, possibly leading to interstitial fibrosis, chronic dysfunction, and finally to a cessation of chemotherapy. There are only a few nephroprotective actions that can help reduce cisplatin nephrotoxicity. This study aims to identify new prophylactic properties with respect to medicinal mushrooms. Among five species, the methanolic extracts of Murill., Welti & Courtec. (10 µg/mL), and their association (5 + 5 µg/mL) were selected to study respective in vitro effects on human proximal tubular cells (HK-2) intoxicated by cisplatin. Measurements were performed after a pretreatment of 1 h with the extracts before adding cisplatin (20 µM). A viability assay, antioxidant activity, intracytoplasmic β-catenin, calcium, caspase-3, p53, cytochrome C, IL-6, NFκB, membranous KIM-1, and ROS overproduction were studied. Tests showed that both methanolic extracts and their association prevented a loss of viability, apoptosis, and its signaling pathway. and the association prevented an increase in intracytoplasmic β-catenin. prevented ROS overproduction and exhibited scavenger activity. None of the extracts could interfere with pro-inflammatory markers or calcium homeostasis. Our in vitro data demonstrate that these mushroom extracts have interesting nephroprotective properties. Finally, the chemical content was investigated through a phytochemical screening, and the determination of the total phenolic and triterpenoid content. Further studies about the chemical composition need to be conducted.
尽管顺铂在许多癌症中被用作一线治疗药物，但其肾毒性仍然是一个实际问题。顺铂诱导的急性肾损伤可导致近端肾小管坏死，可能导致间质纤维化、慢性功能障碍，最终导致化疗中断。目前仅有少数几种肾脏保护措施有助于降低顺铂的肾毒性。本研究旨在确定药用蘑菇的新的预防特性。在五个物种中，选择了Murill.、Welti & Courtec.的甲醇提取物（10μg/mL）及其组合（5 + 5μg/mL），以研究它们对顺铂中毒的人近端肾小管细胞（HK-2）的各自体外作用。在加入顺铂（20μM）之前，先用提取物预处理1小时后进行测量。研究了细胞活力测定、抗氧化活性、胞浆β-连环蛋白、钙、半胱天冬酶-3、p53、细胞色素C、白细胞介素-6、核因子κB、膜性肾损伤分子-1和活性氧过量产生。试验表明，甲醇提取物及其组合均能防止细胞活力丧失、细胞凋亡及其信号通路。并且该组合能防止胞浆β-连环蛋白增加。能防止活性氧过量产生并表现出清除剂活性。没有一种提取物能干扰促炎标志物或钙稳态。我们的体外数据表明，这些蘑菇提取物具有有趣的肾脏保护特性。最后，通过植物化学筛选以及总酚和三萜含量的测定对化学含量进行了研究。需要对其化学成分进行进一步研究。
