Possible Interaction of Oxidative Stress, Inflammatory, and Nitric Oxide Pathways in the Anticonvulsant Effect of Vortioxetine on Pentylenetetrazole-Induced Seizures in Rats

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dc.contributor.authorTaskiran, Ahmet Sevki
dc.contributor.authorFiliz, Ahmet Kemal
dc.date.accessioned2025-05-04T16:46:05Z
dc.date.available2025-05-04T16:46:05Z
dc.date.issued2024
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractAntidepressants are known to demonstrate various effects on the nervous system. As a new antidepressant, vortioxetine is used for major depression in adult patients, with no clear indication of epileptic seizures and underlying mechanisms. The aim here was to examine the impact and possible mechanisms of vortioxetine on pentylenetetrazole-induced epileptic seizures in rats. The rats were randomly divided into 5 groups, each with 6 rats. Group 1 was control, Group 2 was administered saline (1 mL/kg/day serum physiologic), Group 3 was given (1 mg/kg/day diazepam), and Groups 4 and 5 were administered vortioxetine (2.5 and 5 mg/kg/day). The experimental groups (Groups 2-5) were given the drugs for a total of 7 days. Pentylenetetrazole (45 mg/kg) was administered on day 7 to all but the control group. Behavioural testing was performed using passive avoidance and open-field tasks. Total antioxidant status (TAS), total oxidant status (TOS), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP) caspase-3, and caspase-9 levels were measured using a commercial kit. The groups receiving vortioxetine (2.5 and 5 mg/kg) were found to have delayed epileptic seizure onset times and reduced seizure stages with improved memory impairment after seizures. These groups also had increased TAS levels and decreased TOS levels in the cortex and hippocampus. Additionally, TNF-alpha, IL-1 beta, nNOS, sGC, cGMP, caspase-3, and caspase-9 levels in the cortex and hippocampus were statistically significantly lower for these groups. Vortioxetine pretreatment was determined to have protective effects on pentylenetetrazole-induced seizures in rats, with alleviated seizures and improved memory impairment, oxidative stress, inflammation, and apoptosis. The mechanisms of vortioxetine may involve the inhibition of oxidative stress, inflammation, and the nNOS/sGC/cGMP signalling pathway.
dc.description.sponsorshipCumhuriyet University Scientific Research Project (CUBAP, Sivas, Turkey) [T-891]
dc.description.sponsorshipThis study was supported by the Cumhuriyet University Scientific Research Project (No: T-891, CUBAP, Sivas, Turkey).
dc.identifier.doi10.1134/S1819712424700478
dc.identifier.endpage834
dc.identifier.issn1819-7124
dc.identifier.issn1819-7132
dc.identifier.issue4
dc.identifier.scopusqualityN/A
dc.identifier.startpage824
dc.identifier.urihttps://doi.org/10.1134/S1819712424700478
dc.identifier.urihttps://hdl.handle.net/20.500.12418/35348
dc.identifier.volume18
dc.identifier.wosWOS:001447418900021
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.language.isoen
dc.publisherMaik Nauka/Interperiodica/Springer
dc.relation.ispartofNeurochemical Journal
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250504
dc.subjectpentylenetetrazole
dc.subjectvortioxetine
dc.subjectoxidative stress
dc.subjectinflammation
dc.subjectnitric oxide
dc.titlePossible Interaction of Oxidative Stress, Inflammatory, and Nitric Oxide Pathways in the Anticonvulsant Effect of Vortioxetine on Pentylenetetrazole-Induced Seizures in Rats
dc.typeArticle

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