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
  • 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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