کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5738224 | 1615048 | 2017 | 6 صفحه PDF | دانلود رایگان |
- Acute systemic nanocurcumin exerted dose-dependent anticonvulsant properties in PTZ-induced clonic seizure in mice.
- l-arginine as a NO donor prevented the anticonvulsant effects of nanocurcumin. L-NAME and AG potentiated the anticonvulsant effect of sub-effective nanocurcumin.
- NO overproduction probably from iNOS is involved on the seizure susceptibility and suppression of iNOS activity may be one of the possible mechanisms by which nanocurcumin exerts its antiseizure activity.
A plant alkaloid obtained from Curcuma longa, curcumin possesses anti-oxidant and anti-inflammatory effects. Nanoformulations have been developed for preclinical studies which demonstrate enhanced therapeutic efficacy. Effect of acute intraperitoneal (i.p.) administration of curcumin C3 complex nanoparticles [1,5, 10, 20, 40, 80Â mg/kg, (i.p.)] 75Â min prior to PTZ, on clonic seizure thresholds induced by intravenous infusion of pentylenetetrazole (PTZ) 0.5% was investigated in comparison with curcumin (40 and 80Â mg/kg, i.p.) in male mice. Moreover, to clarify the probable role of NO in the anticonvulsant property of nanocurcumin, non-effective doses of l-arginine (l-Arg), a NO donor; 7-nitroindazole, 7-NI, a preferential neuronal NO synthase inhibitor; L-NAME, a non-selective NO synthase inhibitor and aminoguanidine (AG), a selective inducible NO synthase inhibitor (iNOS), in combination with nanocurcumin (80Â mg/kg, i.p.), 15-30Â min before it were employed.ResultsWhile curcumin did not show any anticonvulsant effect, nanocurcumin revealed dose-dependent anticonvulsant property at the doses 20, 40 and 80Â mg/kg, PÂ <Â 0.01, PÂ <Â 0.01 and PÂ <Â 0.001, respectively. l-Arg (30 and 60Â mg/kg) dose-dependently reversed the anticonvulsant effect of the most effective nanocurcumin dose (80Â mg/kg), P<Â 0.01 and P<Â 0.001, respectively. On the other hand, L-NAME (3 and 10Â mg/kg, i.p.) markedly potentiated the sub effective dose of nanocurcumin (10Â mg/kg), PÂ <Â 0.01 and PÂ <Â 0.001, respectively. Similarly, AG (50 and 100Â mg/kg, i.p.) profoundly augmented the seizure thresholds of nanocurcumin (10Â mg/kg), PÂ <Â 0.01 and PÂ <Â 0.001, respectively. In addition, 7-NI (10, 30 and 60Â mg/kg, i.p.) failed to influence the responses.ConclusionThese data may support excess of NO production following PTZ infusion probably resulting from iNOS source. Consequently, nanocurcumin probably down regulated NO. To conclude, nanocurcumin showed anticonvulsant effect. Furthermore, this effect was reversed following l-arginine as an external NO precursor. However, both the non-selective NOS inhibitor and selective iNOS inhibitor increased the thresholds. It is evident that nanocurcumin may influence the seizure thresholds at least in part through a decrease in NO.
Journal: Neuroscience Letters - Volume 651, 9 June 2017, Pages 226-231