RESUMEN
The current study investigated the effects of stevia extracts on a PTZ-induced epileptic rat model and its potential mechanism. Thirty male Sprague-Dawley rats were equally subdivided into 3 groups; (1) normal control (NC) group, (2) PTZ-group: received PTZ (50 mg/kg, i.p. every other day) for 2 weeks, and (3) PTZ+ Stevia group: received PTZ and stevia (200 mg/kg orally daily) for 4 weeks (2 weeks before the start of PTZ treatment and 2 weeks with PTZ administration). The first jerk latency and the seizure score were assessed in rats. Also, brain tissue samples were collected by the end of the experiment, and oxidative stress markers (catalase, MDA, and total antioxidant capacity (TAC)) were measured by biochemical analysis in hippocampal brain homogenates. Also, in the hippocampus, the expression of IL6 and Bcl-2 at the mRNA level and expression of Sirt-1, P53, caspase-3, GFAP, and NF-kB in CA3 hippocampal region by immunohistochemistry was investigated. PTZ substantially increased the seizure score and decreased the seizure latency. Also, PTZ significantly increased MDA, GFAP, IL-6, NF-kB, caspase-3, and p53 and significantly reduced Sirt-1, TAC, and Bcl-2 in hippocampal tissues compared to the control group (p < 0.01). However, Stevia Rebaudiana Bertoni (Stevia R.) significantly attenuated the PTZ-induced seizures, improved oxidative stress markers, downregulated GFAP, IL-6, NF-kB, caspase-3, and p53, and upregulated Sirt-1 and Bcl-2 in the CA3 hippocampal region (p < 0.01). In conclusion, Stevia R. exhibits neuroprotective and antiepileptic actions in PTZ-induced epilepsy due to its antioxidant, anti-apoptotic, and anti-inflammatory effects. Additionally, the Sirt-1 pathway might be involved in the antiepileptic and neuroprotective effects of stevia in PTZ-kindled epileptic rat model.
Asunto(s)
Anticonvulsivantes/farmacología , Antioxidantes/farmacología , Epilepsia/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Extractos Vegetales/farmacología , Stevia , Animales , Anticonvulsivantes/administración & dosificación , Antioxidantes/administración & dosificación , Apoptosis , Convulsivantes/farmacología , Modelos Animales de Enfermedad , Epilepsia/inducido químicamente , Epilepsia/inmunología , Epilepsia/metabolismo , Hipocampo/inmunología , Hipocampo/metabolismo , Masculino , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/metabolismo , Pentilenotetrazol/farmacología , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-Dawley , Sirtuina 1/efectos de los fármacos , Sirtuina 1/metabolismoRESUMEN
BACKGROUND: Epilepsy is a common neurological disease that cannot be well controlled by existing antiepileptic drugs. Studies have implicated oxidative stress and inflammation in the pathophysiology of epilepsy. Rhein has a comprehensive pharmacological function in reducing inflammation and can play a neuroprotective role in many neurological diseases, however little is known about its effects on epilepsy. METHODS: A model of acute epilepsy in mice was established using the Pentylenetetrazol (PTZ) ignition method to evaluate the effects of Rhein on the duration and latency of convulsions, and the number and severity of seizures. Modified Neurological Severity Score (mNSS), Rotarod and open-field behavioral task tests were performed to evaluate the neuroprotective effect of Rhein. TUNEL staining was used to assess neuronal damage, and western blot, qPCR and ELISA kits were utilized to determine the expression of inflammatory signaling protein molecules and levels of inflammatory cytokines. RESULTS: In this study, we demonstrate that Rhein delayed the onset of seizures, decreased their severity, and reduced the duration and frequency of seizures in PTZ-induced epileptic mice. Furthermore, we found that Rhein blocked neurological deficits induced by PTZ. In addition, our results show that Rhein inhibited the activation of the TLR4-NFκB signaling pathway and decreased the secretion of the inflammatory cytokines TNF-α, IL-6, IL-1ß, and IL-18. CONCLUSION: Our results suggest that the anticonvulsant and neuroprotective effects of Rhein are achieved by disrupting the processes involved in PTZ acquisition of epilepsy.
Asunto(s)
Antraquinonas/farmacología , Epilepsia/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Animales , Antraquinonas/uso terapéutico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Epilepsia/inducido químicamente , Epilepsia/diagnóstico , Epilepsia/inmunología , Humanos , Masculino , Ratones , FN-kappa B/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Pentilenotetrazol/administración & dosificación , Pentilenotetrazol/toxicidad , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Receptor Toll-Like 4RESUMEN
Epilepsy is considered a major serious chronic neurological disorder, characterized by recurrent seizures. It is usually associated with a history of a lesion in the nervous system. Irregular activation of inflammatory molecules in the injured tissue is an important factor in the development of epilepsy. It is unclear how the imbalanced regulation of inflammatory mediators contributes to epilepsy. A recent research goal is to identify interconnected inflammation pathways which may be involved in the development of epilepsy. The clinical use of available antiepileptic drugs is often restricted by their limitations, incidence of several side effects, and drug interactions. So development of new drugs, which modulate epilepsy through novel mechanisms, is necessary. Alternative therapies and diet have recently reported positive treatment outcomes in epilepsy. Vitamin D (Vit D) has shown prophylactic and therapeutic potential in different neurological disorders. So, the aim of current study was to review the associations between different brain inflammatory mediators and epileptogenesis, to strengthen the idea that targeting inflammatory pathway may be an effective therapeutic strategy to prevent or treat epilepsy. In addition, neuroprotective effects and mechanisms of Vit D in clinical and preclinical studies of epilepsy were reviewed.
Asunto(s)
Epilepsia/tratamiento farmacológico , Epilepsia/inmunología , Neuroinmunomodulación/fisiología , Animales , Antiinflamatorios/uso terapéutico , Anticonvulsivantes/uso terapéutico , Encéfalo/metabolismo , Citocinas/inmunología , Epilepsia/fisiopatología , Humanos , Inflamación/tratamiento farmacológico , Fármacos Neuroprotectores , Prostaglandina-Endoperóxido Sintasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Resultado del Tratamiento , Vitamina D/metabolismo , Vitamina D/uso terapéuticoRESUMEN
AIMS: This study was designed to investigate if folate treatment is able to reverse the phenytoin-induced deficiency of salivary immunoglobulin A (IgA). METHODS AND MATERIAL: Twenty-five epileptic patients who had been under phenytoin therapy for at least the last 6 months were randomly selected and subjected to folic acid supplementation, 1 mg/day. The salivary IgA concentration of these patients was measured before and after 2 months of folic acid administration and compared with those of 10 healthy individuals. Independent and paired Student's t tests were used to analyze the effects of phenytoin and folic acid, respectively. RESULTS: Salivary IgA levels of patients receiving phenytoin (11.7 +/- 4.8 IU/l) were significantly (p = 0.039) lower than those of healthy controls (14.8 +/- 3.2 IU/l), but did not statistically (p = 0.541) differ from levels (11.8 +/- 4.6 IU/l) measured after 2 months of folic acid supplementation. CONCLUSIONS: According to these results, folic acid supplementation does not seem to have the efficacy to ameliorate phenytoin-induced salivary IgA hyposecretion.
Asunto(s)
Suplementos Dietéticos , Epilepsia/tratamiento farmacológico , Epilepsia/inmunología , Ácido Fólico/administración & dosificación , Deficiencia de IgA/prevención & control , Fenitoína/efectos adversos , Saliva/inmunología , Femenino , Humanos , Deficiencia de IgA/inducido químicamente , Deficiencia de IgA/inmunología , Masculino , Persona de Mediana Edad , Fenitoína/farmacología , Resultado del TratamientoRESUMEN
The immune adherence function of red blood cells in 17 rats was studied. It was found that the rosette rate of red blood cell C3b receptor (RBC-C3bRR) was 7.45 +/- 1.36% in the epilepsy group (8 rats), and 10.84 +/- 1.77% in the control group (9 rats); and that the rosette rate of red blood cell immune complex (RBC-ICR) was 7.42 +/- 2.62% in the epilepsy, and 10.80 +/- 1.72% in the control. As compared with the control group, the rosette rate of red blood cell C3b receptor was remarkably decreased in the epilepsy group (P < 0.05). There was no significant difference between the two groups in RBC-ICR. The results from this study demonstrated that the CL-induced seizures might result in decrease in red blood cell immune adherence function of the epilepsy rats.
Asunto(s)
Epilepsia/inmunología , Eritrocitos/inmunología , Animales , Complejo Antígeno-Anticuerpo/inmunología , Medicamentos Herbarios Chinos , Epilepsia/inducido químicamente , Reacción de Inmunoadherencia , Lactonas , Masculino , Ratas , Ratas Sprague-Dawley , Receptores de Complemento 3b/inmunología , Formación de RosetaRESUMEN
Morphological and immunological assays were employed to examine 18 epileptic patients and 40 Krushinskii-Molodkina rats undergoing subconvulsive and convulsive acoustic stimulations. After multiple audiogenic epileptiform convulsive fits the epileptogenic areas of the brain of epileptic patients (biopsy material) and the neocortex of the sensorimotor area, amygdaloid complex and hippocampus of rats manifested vascular alterations in the form of chronic or subacute vasculitis. The changes revealed in the ratio of B and T lymphocytes in the peripheral blood of the epileptic patients in combination with pronounced stimulation of cellular and humoral immunity responses to antigens of homologous and autologous brain extracts, more well-defined in marked inflammatory process, may attest to the immune genesis of endo- and perivasculitis.
Asunto(s)
Epilepsia/patología , Estimulación Acústica , Animales , Complejo Antígeno-Anticuerpo/análisis , Biopsia , Inhibición de Migración Celular , Epilepsia/inmunología , Humanos , Inmunoglobulinas/análisis , Pruebas de Precipitina , Ratas , Ratas Endogámicas , Formación de Roseta , Convulsiones/inmunología , Convulsiones/patología , Lóbulo Temporal/inmunología , Lóbulo Temporal/patologíaRESUMEN
The levels of circulating immune complexes (CIC) in the peripheral blood were studied in 31 epileptic patients and 30 rabbits which served as an experimental model of the development of the epileptic process. CIC levels in the blood serum were measured by means of polyethylene glycol precipitation followed by measurement of optic density by a spectrophotometer. Elevated concentrations of CIC in the patients' blood were observed in the period of the epileptic status and during a series of epileptic attacks, as well as in experimental animal during epileptic attacks and in the period preceding their development. Blood analysis made at different periods after controlling the attacks showed gradual normalization of the levels of CIC. The role of CIC in the development and maintenance of epileptic seizures is discussed.