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

• Published in: International immunopharmacology Vol. 131; p. 111859
• Main Authors: Murugan, Raghul, Ramya Ranjan Nayak, S.P., Haridevamuthu, B., Priya, D., Chitra, Vellapandian, Almutairi, Bader O., Arokiyaraj, Selvaraj, Saravanan, Muthupandian, Kathiravan, M.K., Arockiaraj, Jesu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.04.2024
• Subjects: Animals; Benzenesulfonamides; COX-2 inhibitor; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Disease Models, Animal; Epilepsy; Epilepsy - chemically induced; Epilepsy - drug therapy; Epilepsy - metabolism; Humans; Neuroinflammation; Neuroprotection; Pentylenetetrazole; Pyrazole; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Zebrafish; Neuroprotection; Neuroinflammation; COX-2 inhibitor; Epilepsy; Pyrazole
• DOI: 10.1016/j.intimp.2024.111859
• ISSN: 1567-5769

[Display omitted] •Pyrazole benzenesulfonamide derivative T1 inhibits COX-2 targeted intervention.•T1 shields against PTZ-induced cellular damage, affirming neuroprotective effects.•The convulsive response in PTZ-exposed zebrafish was ameliorated by T1 treatment.•Gene expression and neutral red assay highlight T1 reduces inflammatory response. 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.