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1.
Brain Res ; 1673: 78-85, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28818511

RESUMO

Despite long use of antiepileptic drugs, it remains a challenge to achieve seizure control while reducing adverse effects and preventing cognitive impairment. Several lines of evidence suggest a role of vitamin D in epilepsy. So this study aimed to investigate the effect of vitamin D on epileptogenesis, cognitive dysfunction and antiepileptic activity of lamotrigine, in a rat model of chemical kindling. Rats were kindled by pentylenetetrazole injections every other day over four weeks, together with daily oral treatment by either vehicle, vitamin D, lamotrigine or combination of vitamin D and lamotrigine. The non-treated kindled rats developed generalized seizures and had poor cognitive performance in water maze, associated with prooxidative status; elevated malondialdehyde and nitric oxide with lowered glutathione levels; in brain tissues. Treatment with either vitamin D, lamotrigine or both leads to significant reduction of seizure activity score, improvement of cognitive performance, and amelioration of the disturbed oxidative stress biomarkers. These findings indicate that, vitamin D has anti-epileptic, cognitive improving and antioxidant effects, on its own and enhance the effects of lamotrigine, in a chronic model of epileptic seizures. Thus, vitamin D supplementation may be a useful addition to antiepileptic drugs improving seizure control and cognitive function in patients with epilepsy.


Assuntos
Anticonvulsivantes/farmacologia , Colecalciferol/farmacologia , Cognição/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Nootrópicos/farmacologia , Triazinas/farmacologia , Animais , Antioxidantes/farmacologia , Doença Crônica , Cognição/fisiologia , Modelos Animais de Doenças , Quimioterapia Combinada , Epilepsia/fisiopatologia , Epilepsia/psicologia , Glutationa/metabolismo , Excitação Neurológica/efeitos dos fármacos , Excitação Neurológica/fisiologia , Lamotrigina , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Pentilenotetrazol , Distribuição Aleatória , Ratos Wistar
2.
Naunyn Schmiedebergs Arch Pharmacol ; 390(10): 977-985, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28687854

RESUMO

Status epilepticus (SE) is considered one of the major serious forms of epilepsy with high mortality rate. Since the currently available antiepileptic drugs have low efficacy and high adverse effects, new more efficient and safe therapies are critically needed. There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Recent studies have shown significant prophylactic and therapeutic potential of vitamin D (vit-D) use in many neurological disorders. Therefore, in the present study, the neuroprotective effects and mechanisms of vit-D alone or in combination with lamotrigine have been evaluated in the lithium-pilocarpine model of SE in rats. Rats were divided into five groups: normal group, SE group, lamotrigine (25 mg/kg/day) pretreated group, vit-D (1.5 mcg/kg/day) pretreated group, and group pretreated with vit-D and lamotrigine for 2 weeks. At the end of treatment, SE was induced by single intraperitoneal injection of LiCl (127 mg/kg), followed 24 h later by pilocarpine (30 mg/kg). Seizures' latency, cognitive performance in Morris water maze, brain oxidative stress biomarkers (glutathione, lipid peroxides, and nitric oxide), brain neurochemistry (γ-aminobutyric acid and glutamate), and brain histopathology have been evaluated. Vit-D prevented pilocarpine-induced behavioral impairments and oxidative stress in the brain; these results were improved in combination with lamotrigine. Vit-D has a promising antiepileptic, neuroprotective, and antioxidant effects. It can be provided to patients as a supportive treatment besides antiepileptic drugs. However, clinical trials are needed to establish its efficacy and safety.


Assuntos
Anticonvulsivantes/administração & dosagem , Cloreto de Lítio/toxicidade , Fármacos Neuroprotetores/administração & dosagem , Pilocarpina/toxicidade , Estado Epiléptico/prevenção & controle , Triazinas/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Modelos Animais de Doenças , Quimioterapia Combinada , Lamotrigina , Masculino , Ratos , Ratos Wistar , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Resultado do Tratamento
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