RESUMO
OBJECTIVE: The aim of study was to investigate the effect of avanafil, a second-generation phosphodiesterase-5 (PDE5) inhibitor, on cerebral ischemia reperfusion (CI/R) model. METHODS: 32 male albino Wistar rats were used. Four groups were constituted, as I: the healthy (sham), II: the CI/R group, III: the CI/R +I 10 mg/kg avanafil group, and IV: the CI/R + 20 mg/kg avanafil group. Avanafil was administered twice via oral gavage, first shortly after ischemia reperfusion and once more after 12 h. The rats were euthanized after 24 h. Histopathological and Real Time PCR analyzes were performed on cerebral tissues. RESULTS: IL-1ß, NLRP3 and TNF-α mRNA expressions were statistically higher in the CI/R group when compared to healthy (sham) group. Conversely, the IL-1ß, NLRP3, and TNF-α mRNA expressions were significantly decreased in both of the avanafil-treated groups when compared to CI/R group. Histopathological results showed that both doses of avanafil also decreased cellular damage in cerebral tissue that occurred after CI/R. CONCLUSION: Avanafil, was found to have ameliorated inflammatory response and cellular injury caused by CI/R. The mRNA expression of IL-1ß, NLRP3, and TNF-α decreased in the I/R groups and approached the control group levels with a high dose of avanafil.
Assuntos
Isquemia Encefálica , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Pirimidinas , Ratos Wistar , Traumatismo por Reperfusão , Animais , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Inflamassomos/metabolismo , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêuticoRESUMO
BACKGROUND: Benidipine is an L, N and T type calcium channel blocker drug that is widely used as an antihypertensive drug. OBJECTIVE: For the first time in the literature, it was aimed to investigate the effectiveness of benidipine in controlling epileptic seizure and preventing the development of neurodegeneration in epilepsy. METHODS: An experimentally epilepsy model was produced with pentylenetetrazole, and rats were divided into seven groups, in different benidipine treatment doses or with valproic acid combinations. The epileptic activities of all rats were recorded according to the Fisher&Kittner classification. Biochemical parameters, histopathological Caspase-3 activity, Wyler hippocampal sclerosis, gliosis and neuronal degenerations were investigated. RESULTS: It was found that in the post-hoc analysis of epileptic activities, there was a similar antiepileptic scores among the treatment groups. IL-1 level was found to be significantly lower in the benidipine 4 mg/kg group, and TNF-alpha was lower in the group given valproic acid+benidipine 2 mg/kg (p<0.05). The other biochemical parameters were not found to be significant. Neural degeneration levels in the brain tissues were statistically significant (p<0.001). Compared with the healthy group, the most neural degeneration was in the control group, the least neural degeneration was in the valproic acid+benidipine 4 mg/kg group. CONCLUSIONS: For the first time in the literature, benidipine, alone or combined with valproic acid, were found to have a statistically significant antiepileptic efficacy, and provided neuroprotection when combined with valproic acid. Benidipine will be a promising agent in the treatment of epilepsy with its antiepileptic and neuroprotective effects.
