WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Deferoxamine Attenuates Seizure Stages, Oxidative Stress, and Apoptosis via Iron Chelation in a PTZ-Induced Epilepsy Model(Pleiades Publishing Ltd, 2026) Cetindag, Arzuhan; Hacisuleyman, LeventRecent evidence suggests that excessive iron accumulation contributes to oxidative stress and neuronal injury, which is a key factor in epilepsy development. To address this, our study evaluated the effects of deferoxamine (DFO), an iron chelator, on seizure severity, oxidative stress, and apoptosis in a rat model of epilepsy triggered by pentylenetetrazole (PTZ). Eighteen male Wistar albino rats were randomly allocated into three experimental groups: Control, PTZ, and PTZ + DFO. Animals received either DFO (250 mg/kg, i.p.) or saline 30 minutes prior to PTZ administration (45 mg/kg, i.p.). Seizure onset and severity were assessed using Racine's Convulsion Scale. Hippocampal tissues were analyzed for total oxidant status (TOS) and total antioxidant status (TAS) as well as caspase-3 and caspase-9 levels. DFO pretreatment significantly reduced seizure stage and prolonged the latency to both the first myoclonic jerk and generalized tonic-clonic seizures relative to the PTZ group. Biochemical analyses revealed that DFO significantly reduced TOS and increased TAS in hippocampal tissue. Additionally, caspase-3 and caspase-9 levels were significantly lower in the PTZ + DFO group relative to the PTZ group. Deferoxamine attenuates seizure severity and delays seizure onset, likely through mechanisms involving iron chelation, antioxidant defense enhancement, and inhibition of apoptosis. These results highlight DFO's neuroprotective capacity, underscoring its possible utility in the management of epileptic disorders.Article Metformin Attenuates PTZ-Induced Seizures and Cognitive Impairment and Is Associated with Altered NOS/NO Signaling: Combined in Vivo and in Silico Evidence(Taylor & Francis Ltd, 2026) Ciltas, Arzuhan Cetindag; Sahin, Bilal; Hacisuleyman, Levent; Çetindağ Çiltaş, ArzuhanBackground: Epilepsy remains a major neurological disorder with high rates of drug resistance and cognitive decline. Repurposing neuroprotective drugs offers a promising approach. Metformin, a widely used antidiabetic agent, has shown anticonvulsant effects, yet its impact on nitric oxide synthase (NOS) isoforms in distinct brain regions remains unclear. Methods: Adult male Wistar rats were allocated into control, pentylenetetrazole (PTZ), or metformin+PTZ groups. Metformin (200 mg/kg, i.p.) was administered for 7 days before induction of acute PTZ seizures (45 mg/kg, i.p.). Seizure severity and latency were assessed using Racine's scale, and cognition was evaluated by the passive avoidance test (PAT). Nitric oxide (NO) and the expression of its synthesizing enzymes, inducible (iNOS), neuronal (nNOS), and endothelial (eNOS), were quantified in the cortex and hippocampus via enzyme-linked immunosorbent assay (ELISA). In silico analyses included target prediction and molecular docking to assess metformin - NOS interactions. Results: Metformin significantly reduced seizure severity, prolonged latency to the first myoclonic jerk, and prevented PTZ-induced memory impairment (all p < 0.001). These behavioral effects were accompanied by reductions in cortical and hippocampal nNOS and iNOS expression, decreased cortical eNOS levels, and lower NO accumulation. TargetNet predicted NOS isoforms among potential metformin targets, and docking indicated moderate binding affinity (-5.2 to -5.9 kcal/mol). Conclusion: Metformin exerted seizure-suppressing and cognition-preserving effects in an acute PTZ model, associated with reductions in NOS isoform expression and NO levels, suggesting altered NOS/NO signaling and supporting its potential as an adjunctive candidate for mitigating seizure-related neuronal dysfunction.