Neuroprotective Potential of Intranasally Delivered Sulforaphane-Loaded Iron Oxide Nanoparticles Against Cisplatin-Induced Neurotoxicity

Abstract

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 (Fe3O4-NPs) could be used as drug carriers. This study aimed to explore the nanotoxic influence of SF-loaded within Fe3O4-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 6th 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 Fe3O4-NPs.

Iron oxide nanoparticles: a narrative review of in-depth analysis from neuroprotection to neurodegeneration

“…The intranasal administration of N.SF to the CIStreated rats were found to have neuroprotective functions on the biochemical, histopathological (striatum and cerebral cortex), and behavioral aspects. 40 Other studies have shown the neuroprotective efficacy of Fe 3 O 4 -NPs in fruit y models by executing catalase-like functions. Its neuroprotective roles have been established in PD and AD models in Drosophila.…”

Natural products for the treatment of chemotherapy-related cognitive impairment and prospects of nose-to-brain drug delivery

“…Besides, another clinical trial conducted in China on the treatment of SFN in AD patients is still ongoing (NCT04213391). In terms of the neuroprotective effects of SFN on chemobrain, recent research has shown that SFN-loaded within iron oxide nanoparticles (SFN-Fe 3 O 4 ) via intranasal administration significantly alleviated cisplatin induced neurotoxicology ( Ibrahim Fouad et al, 2022 ). Furthermore, treatment with SFN-Fe 3 O 4 significantly restored GSH and NO contents as well as inhibited the levels of lipid peroxidation (LPO) in rat brain tissues ( Ibrahim Fouad et al, 2022 ).…”

Synergistic Antineoplastic and Immunomodulatory Effects of Hesperidin in Ehrlich Ascites Carcinoma Tumor Model Treated with Cisplatin

“…Chemotherapeutics are the most common and powerful drugs used in elimination of rapidly proliferating tumor cells even in sites far from their primary origin (Schirrmacher, 2019;Sarbaz et al, 2022). The use of chemotherapeutics is clinically limited due to their severe side and toxic effects in recipient body during treatment of malignant tumors (Liu et al, 2016;Brown et al, 2019;Aliwaini et al, 2020;Zavattaro et al, 2021;Fouad et al, 2022).…”