Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, 12622, Egypt.
Refractories, Ceramics and Building Materials Department, Advanced Materials Technology and Mineral Resources Research Institute, National Research Centre, 33 El Bohouth St., Dokki, Cairo, 12622, Egypt.
Neurotox Res. 2022 Oct;40(5):1479-1498. doi: 10.1007/s12640-022-00555-x. Epub 2022 Aug 15.
Cisplatin (CIS) is a platinum-based chemotherapeutic drug that is widely used to treat cancer. However, its therapeutic efficiency is limited due to its potential to provoke neurotoxicity. Sulforaphane (SF) is a natural phytochemical that demonstrated several protective activities. Iron oxide nanoparticles (FeO-NPs) could be used as drug carriers. This study aimed to explore the nanotoxic influence of SF-loaded within FeO-NPs (N.SF), and to compare the neuroprotective potential of both N.SF and SF against CIS-induced neurotoxicity. N.SF or SF was administrated intranasally for 5 days before and 3 days after a single dose of CIS (12 mg/kg/week, i.p.) on the 6 day. Neuromuscular coordination was assessed using hanging wire and tail-flick tests. Acetylcholinesterase (AChE) activities and markers of oxidative stress were measured in the brain. In addition, the brain iron (Fe) content was estimated. CIS significantly induced a significant increase in AChE activities and lipid peroxides, and a significant decrement in glutathione (GSH) and nitric oxide (NO) contents. CIS elicited impaired neuromuscular function and thermal hyperalgesia. CIS-induced brains displayed a significant reduction in Fe content. Histopathological examination of different brain regions supported the biochemical and behavioral results. Contradict, treatment of CIS-rats with either N.SF or SF significantly decreased AChE activity, mitigated oxidative stress, and ameliorated the behavioral outcome. The histopathological features supported our results. Collectively, N.SF demonstrated superior neuroprotective activities on the behavioral, biochemical, and histopathological (striatum and cerebral cortex) aspects. N.SF could be regarded as a promising "pre-clinical" neuroprotective agent. Furthermore, this study confirmed the safe toxicological profile of FeO-NPs.
顺铂（cisplatin，cis）是一种广泛用于治疗癌症的基于铂的化疗药物。然而，由于其引发神经毒性的潜力，其治疗效率有限。萝卜硫素（sulforaphane，SF）是一种天然植物化学物质，具有多种保护作用。氧化铁纳米颗粒（iron oxide nanoparticles，FeO-NPs）可用作药物载体。本研究旨在探讨负载于 FeO-NPs 中的 SF（N.SF）的纳米毒性影响，并比较 N.SF 和 SF 对顺铂诱导的神经毒性的神经保护潜力。在单次顺铂（12mg/kg/周，腹腔注射）给药前 5 天和后 3 天，通过鼻腔给予 N.SF 或 SF，共 5 天，在第 6 天。使用悬挂线和尾巴敲击试验评估神经肌肉协调性。在大脑中测量乙酰胆碱酯酶（acetylcholinesterase，AChE）活性和氧化应激标志物。此外，还估计了大脑中的铁（Fe）含量。顺铂显著增加 AChE 活性和脂质过氧化物，降低谷胱甘肽（glutathione，GSH）和一氧化氮（nitric oxide，NO）含量。顺铂引起神经肌肉功能障碍和热痛觉过敏。顺铂诱导的大脑中铁含量显著减少。不同脑区的组织病理学检查支持生化和行为结果。相反，用 N.SF 或 SF 治疗 CIS 大鼠可显著降低 AChE 活性，减轻氧化应激，并改善行为结果。组织病理学特征支持我们的结果。总之，N.SF 在行为、生化和组织病理学（纹状体和大脑皮层）方面表现出更好的神经保护作用。N.SF 可以被认为是一种有前途的“临床前”神经保护剂。此外，本研究证实了 FeO-NPs 的安全毒理学特征。
