ML-171 Attenuates Pentylenetetrazole-Associated Oxidative and Apoptotic Injury Without Robust Suppression of Seizure Expression: An In Vitro and In Vivo Study.

Oxidative stress and apoptosis contribute to seizure-associated neuronal injury, but the effects of ML-171, a pharmacological NOX-1 inhibitor, on PTZ-associated oxidative and apoptotic injury remain insufficiently defined. This study evaluated the effects of the NOX-1 inhibitor ML-171 in pentylenetetrazole (PTZ)-induced cellular and animal models of neuronal injury. SH-SY5Y cells were exposed to PTZ (30 mM, 24 h) after pretreatment with ML-171 or valproic acid (VPA), and cell viability, redox status, apoptosis-related proteins, and Annexin V-based cell death were assessed. Adult male Wistar Albino rats were subjected to PTZ kindling and acutely treated with VPA or ML-171 (0.1, 1, or 10 mg/kg); behavioral seizures, electrocorticographic activity, hippocampal oxidative stress, apoptotic markers, histopathology, and NOX-1 immunoreactivity were evaluated. ML-171 attenuated PTZ-induced cellular injury in SH-SY5Y cells within a restricted concentration window and reduced oxidant burden, oxidative stress index, and apoptotic signaling. In PTZ-kindled rats, ML-171 improved hippocampal oxidative and apoptotic markers but did not robustly suppress behavioral or electrophysiological seizure parameters. Histopathological injury and NOX-1 immunoreactivity showed region- and dose-dependent responses. These findings suggest that ML-171 primarily attenuates PTZ-associated oxidative and apoptotic injury rather than exerting a conventional antiseizure effect.