ML-171 Attenuates Pentylenetetrazole-Associated Oxidative and Apoptotic Injury Without Robust Suppression of Seizure Expression: An In Vitro and In Vivo Study
International Journal of Molecular Sciences, cilt.27, sa.14, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 27 Sayı: 14
- Basım Tarihi: 2026
- Doi Numarası: 10.3390/ijms27146269
- Dergi Adı: International Journal of Molecular Sciences
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: apoptosis, epilepsy, hippocampus, kindling, ML-171, NADPH Oxidase, NOX-1, oxidative stress, pentylenetetrazole, SH-SY5Y cells
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
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.