RESUMEN
Sparteine is one of the most toxic quinolizidine alkaloids found in leguminous plants. Several studies have demonstrated that sparteine affects the nervous system, blocking the nervous ganglion, producing antimuscarinic effects, depressing the central nervous system and causing neuronal necrosis. However, there are no reports identifying the areas of the brain that are sensitive to the toxic effects of this alkaloid. 32 adult Wistar rats were on study, sixteen were implanted with an intracerebral stainless steel cannula and randomly assigned to a control or experimental group (n=8). Animals, control and experimental, received daily intraventricular (ICV) injections of a sparteine or a sterile water solution for five consecutive days. Additionally, two groups of animals (8 rats each) received daily intraperotineal injections (IP) of a sparteine or sterile water solution for five consecutive days. 72h after the last dose, the animals were sacrificed, their brains removed, fixed and embedded in paraffin to obtain 10µm tissue slices. Brain slices were stained with H&E and evaluated under a light microscope. The main brain structures sensitive to sparteine were the cerebral cortex (frontal, fronto-parietal and striate) olfactory and amygdaloid areas, the ventromedial hypothalamic nucleus, the Purkinje cells in the cerebellum, and the CA1, CA3 and dentate gyrus regions of the hippocampus. Administration of sparteine, via ICV or IP, caused neuronal necrosis in brain structures, mainly related with cholinergic pathways.
Asunto(s)
Antiarrítmicos/toxicidad , Encéfalo/efectos de los fármacos , Encéfalo/patología , Esparteína/toxicidad , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas WistarRESUMEN
Sparteine is a quinolizidine alkaloid extracted from Lupinus that has numerous pharmacological properties both in humans and animal models. In the central nervous system, sparteine reduces locomotor activity, has light analgesic effects, also has no effects on short-term memory or spatial learning and does not induce changes in behavior or electroencephalographic (EEG) activity. However, the anticonvulsant profile of sparteine is not fully characterized in experimental animals and there are no data in humans. Therefore, the present review focuses on the experimental evidence supporting the anticonvulsant action of sparteine in models of acute seizures and status epilepticus (SE), as well as its possible mechanisms of action. The evidence that supports the anticonvulsant effect of (-)-Sparteine sulfate includes the inhibition of seizures induced by maximal electro-stimulation, a delay in the onset of convulsive behavior and the prolongation of survival time in mice treated with pentylenetetrazole (PTZ). Additionally, sparteine delays the onset of convulsive behavior and decreases the severity and mortality of rats treated with PTZ and pilocarpine. Sparteine decreases amplitude and frequency or blocks the epileptiform activity induced by PTZ, pilocarpine and kainic acid. Sparteine may decrease hyperexcitability through the activation of the M2 and M4 subtypes of mAChRs, which is a probable mechanism of action that together with its systemic effects may favor its anticonvulsant effects against seizures and SE.
Asunto(s)
Anticonvulsivantes/farmacología , Convulsiones/tratamiento farmacológico , Esparteína/farmacología , Estado Epiléptico/tratamiento farmacológico , Animales , Anticonvulsivantes/toxicidad , Esparteína/toxicidadRESUMEN
Sparteine is a quinolizidine alkaloid (QA) produced by Lupine species that has generated much interest due to its anti-hypertensive, anti-pyretic, and anti-inflammatory properties. In the nervous system, sparteine has been shown to display anti-cholinergic and depressive activity, although how sparteine exerts its toxic effects in the brain remains unclear. We have addressed this issue by administering subcutaneous injections of sparteine (25 mg/kg of body weight) to rats on postnatal days 1 and 3, and then examining the expression of the muscarinic acetylcholine receptor (mAChR) subunits m1-m4 in the brains of the neonatal rats 14-60 days later. Administration of sparteine to neonatal rats caused neuronal damage in the cerebral motor cortex accompanied by transient changes in the expression of m1-m4 mAChR subunits as revealed by both RT-PCR and Western blotting. This effect could be prevented by pre-treatment with atropine (10 mg/kg) 1 h prior to the injection of sparteine, suggesting that the cytotoxic activity of sparteine is mediated through mAChRs.