PUBLICATION

Neuroprotective potential of pyrazole benzenesulfonamide derivative T1 in targeted intervention against PTZ-induced epilepsy-like condition in in vivo zebrafish model

Authors
Murugan, R., Ramya Ranjan Nayak, S.P., Haridevamuthu, B., Priya, D., Chitra, V., Almutairi, B.O., Arokiyaraj, S., Saravanan, M., Kathiravan, M.K., Arockiaraj, J.
ID
ZDB-PUB-240317-5
Date
2024
Source
International Immunopharmacology   131: 111859111859 (Journal)
Registered Authors
Keywords
COX-2 inhibitor, Epilepsy, Neuroinflammation, Neuroprotection, Pyrazole
MeSH Terms
  • Zebrafish
  • Humans
  • Disease Models, Animal
  • Cyclooxygenase 2/genetics
  • Cyclooxygenase 2/metabolism
  • Pentylenetetrazole*
  • Pyrazoles/pharmacology
  • Pyrazoles/therapeutic use
  • Animals
  • Benzenesulfonamides
  • Epilepsy*/chemically induced
  • Epilepsy*/drug therapy
  • Epilepsy*/metabolism
(all 13)
PubMed
38492342 Full text @ Int. Immunopharmacol.
Abstract
Epilepsy is a chronic neurological disease characterized by a persistent susceptibility to seizures. Pharmaco-resistant epilepsies, impacting around 30 % of patients, highlight the urgent need for improved treatments. Neuroinflammation, prevalent in epileptogenic brain regions, is a key player in epilepsy, prompting the search for new mechanistic therapies. Hence, in this study, we explored the anti-inflammatory potential of pyrazole benzenesulfonamide derivative (T1) against pentylenetetrazole (PTZ) induced epilepsy-like conditions in in-vivo zebrafish model. The results from the survival assay showed 79.97 ± 6.65 % at 150 µM of T1 compared to PTZ-group. The results from reactive oxygen species (ROS), apoptosis and histology analysis showed that T1 significantly reduces cellular damage due to oxidative stress in PTZ-exposed zebrafish. The gene expression analysis and neutral red assay results demonstrated a notable reduction in the inflammatory response in zebrafish pre-treated with T1. Subsequently, the open field test unveiled the anti-convulsant activity of T1, particularly at a concentration of 150 μM. Moreover, both RT-PCR and immunohistochemistry findings indicated a concentration-dependent potential of T1, which inhibited COX-2 in zebrafish exposed to PTZ. In summary, T1 protected zebrafish against PTZ-induced neuronal damage, and behavioural changes by mitigating the inflammatory response through the inhibition of COX-2.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Murugan, R., Ramya Ranjan Nayak, S.P., Haridevamuthu, B., Priya, D., Chitra, V., Almutairi, B.O., Arokiyaraj, S., Saravanan, M., Kathiravan, M.K., Arockiaraj, J. (2024) Neuroprotective potential of pyrazole benzenesulfonamide derivative T1 in targeted intervention against PTZ-induced epilepsy-like condition in in vivo zebrafish model. International Immunopharmacology. 131:111859111859.