Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, 442 102, India.
Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Uttar Pradesh, Varanasi, 221 005, India.
Acta Parasitol. 2021 Dec;66(4):1212-1221. doi: 10.1007/s11686-021-00394-4. Epub 2021 Apr 21.
Silver nanoparticles (AgNPs) mediated apoptosis is well-known but its rationale is yet to be elucidated. This study explored the mechanistic underpinning of the apoptosis in the Brugia malayi parasitic model.
Silver nanoparticles were synthesized and tested against B. malayi microfilariae (Mf) to explore the role of oxidative and nitrosative stress in its apoptotic effect.
AgNPs caused significant decrease in reduced glutathione (GSH) level and increase in both protein carbonylation and nitric oxide (NO) level indicating oxidative as well as nitrosative stress. Both GSH and nitric oxide synthase (NOS) inhibitors exhibited marked reversal. Nanoparticles and NO-donor in combination but not the NO-donor alone showed significant antiparasitic effect implying the requisite of combined oxidative and nitrosative stress to induce apoptosis. Synthetically prepared peroxynitrite from NaNO to HO showed marked antiparasitic effect in very low dose which could be achieved neither by NaNO or HO alone. GSH reversed the effect of peroxynitrite similar to its specific inhibitor, acetaminophen. GSH also reversed the plummet in mitochondrial oxygen consumption by AgNPs.
We conclude that apoptosis by AgNPs is possibly mediated through peroxynitrite dependent depletion of GSH; this provides a significant insight into the pharmacological as well as toxicological impact of AgNPs.
银纳米粒子（AgNPs）介导的细胞凋亡是众所周知的，但它的原理尚未阐明。本研究探讨了银纳米粒子在曼氏血吸虫寄生模型中诱导细胞凋亡的机制。
合成银纳米粒子并对曼氏血吸虫微丝蚴（Mf）进行测试，以探索氧化应激和硝化应激在其凋亡作用中的机制。
AgNPs 导致还原型谷胱甘肽（GSH）水平显著降低，同时蛋白质羰基化和一氧化氮（NO）水平升高，表明存在氧化应激和硝化应激。GSH 和一氧化氮合酶（NOS）抑制剂均表现出显著的逆转作用。纳米粒子和一氧化氮供体联合使用而非单独使用一氧化氮供体显示出显著的抗寄生虫效果，表明需要联合氧化应激和硝化应激来诱导细胞凋亡。从 NaNO 到 HO 合成制备的过氧亚硝酸盐在非常低的剂量下显示出显著的抗寄生虫效果，这是单独使用 NaNO 或 HO 都无法达到的。GSH 逆转了过氧亚硝酸盐的作用，类似于其特异性抑制剂对乙酰氨基酚。GSH 还逆转了 AgNPs 引起的线粒体耗氧量的急剧下降。
我们得出结论，AgNPs 诱导的细胞凋亡可能是通过依赖于过氧亚硝酸盐的 GSH 耗竭来介导的；这为银纳米粒子的药理学和毒理学影响提供了重要的见解。
