AI Article Synopsis
- Methylphenidate (MPH) abuse may lead to neurodegeneration and increased seizure risks, while topiramate (TPM), an antiepileptic drug, shows promise as a neuroprotective agent against these complications when delivered via nanoparticles.
- The study employed male rats divided into groups receiving MPH and varying doses of TPM and mesoporous silica nanoparticles (MSN) with zinc or copper cores over three weeks, followed by seizure induction to assess neuroprotective effects.
- Results indicated that TPM-loaded nanoparticles significantly improved seizure latency and duration, reduced inflammatory markers and oxidative stress in the hippocampus, suggesting their potential as protective agents against MPH-induced neurotoxicity.
Article Abstract
Background: Methylphenidate (MPH) abuse has been criticized for its role in neurodegeneration. Also, a high risk of seizure was reported in the first month of MPH treatment. Topiramate, a broad-spectrum Antiepileptic Drug (AED), has been used as a neuroprotective agent in both aforementioned complications. Nanotechnology is introduced to increase desirable neurological treatment with minimum side effects. We aimed to investigate the potential neuroprotective activity of topiramate loaded on nanoparticles.
Methods And Results: MTT assay was performed to evaluate the cellular cytotoxicity of Mesoporous Silica Nanoparticles (MSN). Male rats were randomly divided into eight groups. Rats received an intraperitoneal (i.p) MPH (10 mg/kg) injection and a daily oral dose of topiramate (TPM, 30 mg/kg), MSN with Zn core (10 and 30 mg/kg), and MSN with Cu core (10 and 30 mg/kg) for three weeks. On day 21, a seizure was induced by a single injection of pentylenetetrazole (PTZ) to evaluate the protective effects of TPM-loaded nanoparticles on seizure latency and duration following MPH-induced neurotoxicity. Moreover, the hippocampal content of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and the anti-oxidant enzymes (SOD, GPx, and GR) activities were assessed. Also, BAX and Bcl-2 as two main apoptotic markers were evaluated.
Results: MPH neurotoxicity was observed as a raised duration and reduced latency in PTZ-induced seizure. However, TPM-loaded MSN with Zn species (NE) treatment reduced the duration and improved the latency time. Also, NE and, somewhat, TPM-loaded MSN with Cu species (NM) administration reduced inflammatory cytokines, MDA, and Bax levels and increased activities in the rat hippocampus.
Conclusion: TPM-loaded nanoparticles could be used as neuroprotective agents against MPH-induced neurodegeneration by improving seizure parameters and reducing inflammatory, oxidant, and apoptotic factors.
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| http://dx.doi.org/10.1007/s11033-023-09011-1 | DOI Listing |
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