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.
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.
Int Immunopharmacol. 2024 Apr 20;131:111859. doi: 10.1016/j.intimp.2024.111859. Epub 2024 Mar 15.
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.
癫痫是一种慢性神经系统疾病,其特征是持续易患癫痫。约 30%的患者患有药物难治性癫痫,这突出表明需要改进治疗方法。神经炎症是癫痫的一个关键因素,存在于致痫性脑区,这促使人们寻找新的机制治疗方法。因此,在这项研究中,我们在体内斑马鱼模型中探索了吡唑苯磺酰胺衍生物(T1)对戊四氮(PTZ)诱导的癫痫样条件的抗炎潜力。生存试验结果显示,在 150 μM 的 T1 下,存活率为 79.97±6.65%,与 PTZ 组相比。活性氧(ROS)、细胞凋亡和组织学分析的结果表明,T1 可显著减轻 PTZ 暴露的斑马鱼因氧化应激造成的细胞损伤。基因表达分析和中性红试验结果表明,T1 预处理可显著减少斑马鱼的炎症反应。随后,在开放场试验中揭示了 T1 的抗惊厥活性,特别是在 150 μM 的浓度下。此外,RT-PCR 和免疫组织化学结果表明,T1 具有浓度依赖性,可抑制 PTZ 暴露的斑马鱼中的 COX-2。综上所述,T1 通过抑制 COX-2 减轻炎症反应,从而保护斑马鱼免受 PTZ 诱导的神经元损伤和行为改变。
Biomed Pharmacother. 2017-3