EFFECTS OF SILVER NANOPARTICLES ON PENTYLENETETRAZOL-INDUCED KINDLED SEIZURES IN RATS

Abstract

Silver nanoparticles are used for delivering neurotropic agents to brain, increasing the bioavailability of insoluble drugs as well as for brain tumours treatment. Their effects upon brain excitability, especially under conditions of chronic epilepsy modelling are underinvestigated. The purpose of the study was to study the effects of silver nanoparticles upon pentylenetetrazol-induced kindled seizures in rats. Material and Methods. Experiments were performed on Wistar rats kindled during four weeks with pentylenetetrazol administrations in a dose of 30.0 mg/kg, i.p. Only rats, which demonstrated generalized clonic-tonic seizures in a response to each of three last epileptogen injections, were included into the study. Nanoparticles and ionized argentum were administered in a dosage of 0.2 mg/kg, i.p. Observation was performed in early and postponed period of kindling – in 24 h and three weeks from the moment of kindling induction, correspondently. Results and discussion. The calculation of the pentylenetetrazol dose, which effectively induced seizures in 50 % of kindled rats (ED50), was performed in kindled animals in 24 h from the moment of last epileptogen administration was 22.0 mg/kg. In postponed period of kindling (three weeks from the moment of last pentylenetetrazol administration in a dose of 30.0 mg/kg, i.p.), ED50 of pentylenetetrazol was 16.0 mg/kg. ED50 of pentylenetetrazol, which induced clonic seizures in 50 % animals at the early stage of kindling, was recalculated following the administration of ionized and nanoparticle forms of silver, and were less when compared with such ones determined in the control group by 13.5 % (P>0,05) and 26.0 % (P<0,05), respectively. In the postponed period of kindling ED50 of ionized and nanoparticle forms of silver were less when compared with control by 20.0 % (P<0.05) and by 42.0 %, respectively (P<0.05). Significant difference was noted between groups treated with ionized and nanoparticle silver (P<0.05). The net intensification of pentylenetetrazol seizure manifestations was seen in kindled rats treated with silver nanoparticles, when seizure discharges amplitude achieved 1.0-1.2 mV and frequency of 3/sec, which exceeded the ones in rats treated with ionized silver. Conclusion. Silver nanoparticles induce the increase in seizures severity in pentylenetetrazol-kindled rats, and this effect was more pronounced at the postponed stage of kindling development.