Positive effects of angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole-induced epileptic seizures in mice

Abstract

Purpose: To evaluate the effects of an angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole (PTZ)-induced seizures and post-seizure hippocampal injury.
 Materials: Thirty-five male Balb-c mice weighing 30 - 33 g were divided into control, saline PTZ, s(erum physiologic 1 ml/kg as solvent), positive control (valproic acid 200 mg/kg), captopril (25 mg/kg/day for 7 days), and captopril (50 mg/kg/day for 7 days) groups. PTZ (60 mg/kg) was administered thirty minutes after medication administration to induce epileptic seizures. The animals were observed for 30 min to record Racine stages, the time of the first myoclonic jerk (FMJ), and the occurrence of the first generalized tonic-clonic seizure (GTCS). Cornu Ammonis (CA)1, CA2, CA3, and the dentate gyrus (DG) of the hippocampus underwent histopathological examinations. The levels of total oxidant status (TOS), oxidative stress markers (total antioxidant status, TAS), and oxidative stress index (OSI) were measured in the brain tissue.
 Results: Compared to PTZ group, 25 mg/kg captopril decreased seizure scores and delayed FMJ and GTCS (p < 0.05). Histopathological assessment demonstrated that both 25 and 50 mg/kg captopril alleviated neuronal injury in CA1, CA2, CA3, and DG compared to PTZ (p < 0.05). Also, TOS and OSI levels in the brain tissue were reduced by both 25 and 50 mg/kg doses of captopril (p < 0.05).
 Conclusion: Captopril favorably improves epileptic seizure parameters and acts against post-seizure neuronal injury in the hippocampus. Captopril may be a drug of choice in epileptic individuals with hypertension.
 Keywords: Captopril, Angiotensin-converting enzyme, Epilepsy, Pentylenetetrazole, Neuronal damage

The effects of sugammadex on pentylenetetrazole-induced seizures in mice

“…The Modi ed Racine's Convulsion Scale (RCS), which de nes seizure stages as follows, was used to rate the severity of the seizures: 0 = no convulsion; 1 = twitching of vibrissae and pinnae; 2 = motor arrest with more pronounced twitching; 3 = myoclonic jerks; 4 = tonic-clonic seizure while the animal remained on its feet; 5 = tonic-clonic seizure with loss of the righting re ex; 6 = tonicclonic seizure with wild climbing and jumping; and 7 = lethal seizure ). Following PTZ injection, the mice were observed for 30 min to score their behavior according to the RCS, time of the beginning of the rst myoclonic jerk (FMJ), and the onset of the generalized tonic-clonic seizures (oGTCS) (Tastemur et al 2020). The brain tissues were taken from the mice to evaluate biochemical and histological markers, including oxidative stress, autophagy, and apoptosis.…”

“…In seizures, excessive and abnormal electrical discharge from cortical neurons causes a temporary brain dysfunction (Karademir et al 2019). Epilepsy is an abnormal central nervous system condition characterized by recurrent seizures related to a genetic predisposition or pathological disorders (Tastemur et al 2020; Karademir et al 2022). About 1% of the world's population suffers from this neurological disorder (Sevki Taskıran et al 2018).…”

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“…PTZ akut nöbet modeli oluşturmak için farelere önceki çalışmalardan referans alınarak 60 mg/kg'lık (10 ml/kg) tek doz PTZ uygulaması yapıldı. 16 Ayrıca çalışmamızda folik asidin etosüksimidin antikonvülsan etkinliğini güçlendirdiği gösterilmiştir.…”

Sıçanlarda Pentilentetrazol ile İndüklenen Akut Epilepsi Modelinde Valproik Asidin NO/cGMP Üzerindeki Etkileri

“…Epilepsy, one of the neurodegenerative disorders, is reported to be caused by NO. Epilepsy is a neurodegenerative disease that affects 3% of the world population [4] and occurs with recurrent seizures [5].…”