Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmacodynamics and Toxicology, School of Pharmacy; Mashhad University of Medical Sciences, Mashhad, Iran.
J Trace Elem Med Biol. 2023 Dec;80:127291. doi: 10.1016/j.jtemb.2023.127291. Epub 2023 Aug 26.
Several metallic elements with high atomic weight and density are serious systemic toxicants, and their wide environmental distribution increase the risk of their exposure to human. Silymarin (SL), a polyphenol from milk thistle (Silybum marianum) plant has shown protective role against heavy metal toxicity. However, its low aqueous solubility and rapid metabolism limits its therapeutic potential in clinic.
We compared the role of silymarin nanoliposomes (SL-L) against cadmium (Cd) toxicity in normal MRC-5 and A 549 cancer cells. MRC-5 and A 549 cells exposed to Cd at 25 and 0.25 µM respectively, were treated with various non-toxic SL-L concentrations (2.5, 5, 10 µM) and cells viability, reactive oxygen species (ROS) generation, apoptosis and levels of cleaved PARP and caspase-3 proteins were determined following incubation.
Results indicated that Cd exposure significantly increased apoptosis due to ROS generation, and showed greater toxicity on cancer cells compared to normal cells. While SL-L at higher concentrations (25 µM and higher) exhibits pro-apoptotic features, lower concentrations (10 and 2.5 µM for MRC-5 and A 549 cancer cells, respectively) played a protective and anti-oxidant role in Cd induced toxicity in both cells. Further, lower SL-L was required to protect cancer cells against Cd toxicity. In general, treatment with SL-L significantly improved cell survival by decreasing ROS levels, cleaved PARP and caspase-3 in both MRC-5 and A 549 cells compared to free silymarin.
Results demonstrated that SL-L potential in protecting against Cd-induced toxicity depends on concentration-dependent antioxidant and anti-apoptotic balance.
几种原子量和密度高的金属元素是严重的全身性毒物，它们广泛存在于环境中，增加了人类接触的风险。水飞蓟素（SL）是一种来自奶蓟（Silybum marianum）植物的多酚，已显示出对重金属毒性的保护作用。然而，其低水溶解度和快速代谢限制了其在临床上的治疗潜力。
我们比较了水飞蓟素纳米脂质体（SL-L）对正常 MRC-5 和 A549 癌细胞中镉（Cd）毒性的作用。将 MRC-5 和 A549 细胞分别暴露于 25 和 0.25µM 的 Cd 下，用各种无毒的 SL-L 浓度（2.5、5、10µM）处理细胞，并在孵育后测定细胞活力、活性氧（ROS）生成、凋亡和裂解 PARP 和 caspase-3 蛋白水平。
结果表明，Cd 暴露会因 ROS 生成而显著增加细胞凋亡，并显示出比正常细胞更大的毒性。而较高浓度（25µM 及更高）的 SL-L 表现出促凋亡特征，而较低浓度（分别为 10 和 2.5µM 的 MRC-5 和 A549 癌细胞）在两种细胞中对 Cd 诱导的毒性具有保护和抗氧化作用。此外，需要较低浓度的 SL-L 来保护癌细胞免受 Cd 毒性的影响。一般来说，与游离水飞蓟素相比，用 SL-L 处理可通过降低 ROS 水平、裂解 PARP 和 caspase-3 来显著提高 MRC-5 和 A549 细胞的存活率。
结果表明，SL-L 对 Cd 诱导的毒性的保护作用取决于浓度依赖性的抗氧化和抗凋亡平衡。
