PUBLICATION
Evaluation of the effects of carbamazepine-loaded chitosan-coated PLGA-Zein nanoparticles on pilocarpine-induced seizure model in zebrafish larvae: Developmental toxicity and behavioral assays
- Authors
- Alak, G., Yıldırım, S., Ugur Kaplan, A.B., Köktürk, M., Nazli, D., Gözegir, B., Ozhan, G., Cetin, M.
- ID
- ZDB-PUB-250118-4
- Date
- 2025
- Source
- Environmental toxicology and chemistry 44: 751-763 (Journal)
- Registered Authors
- Özhan, Günes
- Keywords
- Epilepsy, carbamazepine nanoparticles, developmental toxicity, neurological effects, zebrafish seizure model
- MeSH Terms
-
- Animals
- Anticonvulsants*/toxicity
- Behavior, Animal/drug effects
- Carbamazepine*/toxicity
- Chitosan*/chemistry
- Disease Models, Animal
- Larva*/drug effects
- Nanoparticles*/chemistry
- Nanoparticles*/toxicity
- Pilocarpine*/toxicity
- Polylactic Acid-Polyglycolic Acid Copolymer/chemistry
- Polylactic Acid-Polyglycolic Acid Copolymer/toxicity
- Seizures*/chemically induced
- Zebrafish*
- PubMed
- 39821319 Full text @ Environ. Toxicol. Chem.
Citation
Alak, G., Yıldırım, S., Ugur Kaplan, A.B., Köktürk, M., Nazli, D., Gözegir, B., Ozhan, G., Cetin, M. (2025) Evaluation of the effects of carbamazepine-loaded chitosan-coated PLGA-Zein nanoparticles on pilocarpine-induced seizure model in zebrafish larvae: Developmental toxicity and behavioral assays. Environmental toxicology and chemistry. 44:751-763.
Abstract
Epilepsy, the most common neurological disorder worldwide, is characterized by sudden paroxysmal brain activity, which can be generalized or focal. Extensive research has explored various treatment strategies for this condition. Our study employed a pilocarpine (PL)-induced seizure model in zebrafish (Danio rerio) embryos and larvae to assess the effects of carbamazepine (CBZ)-loaded chitosan-coated PLGA-Zein nanoparticles (NPs) over 96 hours. We evaluated the developmental toxicity (mortality, malformation, and larval hatching), behavioral changes (sensorimotor reflexes), and histopathological and immunohistochemical alterations in brain tissue, focusing on 5-hydroxytryptamine receptor 4 (5HT4), and brain and muscle ARNT-Like 1 (BMAL1) expressions. Our findings revealed high mortality and malformation rates in groups treated with pure CBZ (PL+CBZ 50 and PL+CBZ 100). These groups also exhibited delayed hatching and impaired sensorimotor reflexes. In contrast, the CBZ-NP-treated groups (PL+CBZ NP 50 and PL+CBZ NP 100) showed hatching rates comparable to the control group, with significantly lower mortality and malformation rates compared to pure CBZ-treated groups. Moreover, intense cytoplasmic expression of 5HT4 and BMAL1 was observed in neuropils of the PL+CBZ 100 group. This study highlights the potential of CBZ-loaded NPs in reducing developmental toxicity and adverse neurological effects associated with pure CBZ treatment in seizure models.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping