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

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

  • Int Immunopharmacol. 2024 Mar 15:131:111859. doi: 10.1016/j.intimp.2024.111859.
Raghul Murugan 1,  S P Ramya Ranjan Nayak 1,  B Haridevamuthu 1,  D Priya 2,  Vellapandian Chitra 3,  Bader O Almutairi 4,  Selvaraj Arokiyaraj 5,  Muthupandian Saravanan 6,  M K Kathiravan 7,  Jesu Arockiaraj 8
Affiliations

Affiliations

  • 1 Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India.
  • 2 Dr APJ Abdul Kalam Research Lab, Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India.
  • 3 Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India.
  • 4 Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
  • 5 Department of Food Science & Biotechnology, Sejong University, Seoul 05006, Republic of Korea.
  • 6 AMR and Nanotherapeutics Laboratory, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu 600077, India.
  • 7 Dr APJ Abdul Kalam Research Lab, Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India. Electronic address: [email protected].
  • 8 Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India. Electronic address: [email protected].
PMID: 38492342 DOI: 10.1016/j.intimp.2024.111859
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.

Keywords

COX-2 inhibitor; Epilepsy; Neuroinflammation; Neuroprotection; Pyrazole.

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