Medical Physiology Department, College of Medicine, Zagazig University, Egypt; Medical Physiology Department, Faculty of Medicine, Northern Border University, Saudi Arabia.
Department of Basic Medical Sciences, College of Medicine, Almaarefa University, Ad Diriyah, 13713, Saudi Arabia; Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Neurotoxicology. 2021 Jan;82:167-176. doi: 10.1016/j.neuro.2020.12.008. Epub 2020 Dec 23.
Silver nanoparticles (AgNPs) are widely applied in various aspects of life. However, recent studies reported their potential toxicity both on environment and human health. The present study aimed to unravel the underlying molecular mechanisms involved in AgNPs-induced brain toxicity. Moreover, chemopreventive effect of tranilast, an analogue of tryptophan metabolite and a mast cell membrane stabilizer was evaluated. Thirty Sprague Dawley rats were enrolled equally into Normal control group, AgNPs-intoxicated group (50 mg/kg, 3 times/week) and tranilast (300 mg/kg, 3 times/week)+AgNPs group. AgNPs administration triggered brain oxidative stress as depicted by reduced Nrf-2 expression, decreased TAC and GSH as well as upregulated brain lipid peroxidation. The apparent brain oxidative damage was accompanied by elevated levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α). Moreover, brain levels of TLR4, NLRP3 and caspase-1 were up-regulated. Additionally, histological study indicated marked cellular injury in cerebrum and cerebellum specimens. This was concomitant with elevated serum CK activity and CK-BB level. On the other hand, tanilast administration remarkably alleviated AgNPs-induced brain toxicity. The present study shed the light on implication of TLR4/NLRP3 axis and NrF2 in AgNPs-induced brain toxicity. In addition, it explored the potential protective effect of tranilast on AgNPs-induced brain injury via antioxidant and anti-inflammatory efficacies.
纳米银颗粒（AgNPs）广泛应用于生活的各个方面。然而，最近的研究报告称，它们对环境和人类健康具有潜在毒性。本研究旨在揭示 AgNPs 诱导的脑毒性的潜在分子机制。此外，还评估了曲尼司特（色氨酸代谢物的类似物和肥大细胞膜稳定剂）的化学预防作用。将 30 只 Sprague Dawley 大鼠平均分为正常对照组、AgNPs 中毒组（50mg/kg，每周 3 次）和曲尼司特（300mg/kg，每周 3 次）+AgNPs 组。AgNPs 给药引发了脑氧化应激，表现为 Nrf-2 表达减少、TAC 和 GSH 减少以及脑脂质过氧化增加。明显的脑氧化损伤伴随着炎症细胞因子（IL-1β、IL-6 和 TNF-α）水平的升高。此外，脑内 TLR4、NLRP3 和 caspase-1 的水平也升高。此外，组织学研究表明大脑和小脑标本中存在明显的细胞损伤。这与血清 CK 活性和 CK-BB 水平的升高相一致。另一方面，曲尼司特给药显著减轻了 AgNPs 诱导的脑毒性。本研究揭示了 TLR4/NLRP3 轴和 NrF2 在 AgNPs 诱导的脑毒性中的作用。此外，它还通过抗氧化和抗炎作用探讨了曲尼司特对 AgNPs 诱导的脑损伤的潜在保护作用。
