Abstract
Purpose: To investigate the protective effect of baicalein against chronic seizures in pentylenetetrazole induced epilepsy in a rat model.Methods: A rat model of chronic epilepsy was prepared by administration of pentylenetetrazole at a dose of 35 mg/kg to Sprague-Dawley rats. The animals were divided into 6 groups (5 rats/group): normal control, model (untreated epilepsy) and four treatment groups that received separately, intraperitoneal injection of 20, 30, 40 and 50 mg/kg baicalein, respectively, on alternate days for 30 days. On each day following baicalein treatment, behavioural alterations in the rats were assessed.Results: Analyses of behavioural changes revealed significant (p < 0.05) decrease in pentylenetetrazole-induced convulsions by baicalein treatment at a dose of 50 mg/kg. Immunohistochemical studies revealed that treatment with baicalein caused significant (p < 0.05) dosedependent reductions in the levels of inducible nitric oxide synthase (iNOS). Baicalein treatment inhibited alterations in cell morphology, and also inhibited pentylenetetrazole-induced increase in the proportion of glial fibrillary acidic protein (GFAP)-positive cells in a dose-dependent manner (p < 0.05). Real-time polymerase chain reaction (RT-PCR) analysis showed that baicalein significantly inhibited the expression of mRNA of NR1 subunit N methyl D aspartic acid (NMDA) receptor, without any effect on the expression of the NR2b (N-methyl D-aspartate receptor subtype 2B ) subunit mRNA (p < 0.05).Conclusion: These results indicate that baicalein inhibits pentylenetetrazole-induced chronic seizures in rats via reduction in astrocytes, inhibition of neuronal death and reduction of NR1 mRNA expression. Thus, baicalein has a potential for development into a new drug for the treatment of chronic epilepsy.Keywords: Pentylenetetrazole, Epilepsy, Baicalein, Convulsion, Inhibition, behavioural changes, Hippocampus
Highlights
The flavone, 5, 6, 7-trihydroxyflavone, known as baicalein (Figure 1), is a natural isolate obtained from Scutellaria baicalensis Georgi
A known fivepoint scale [11] was used for the analysis of the effect of baicalein on convulsions caused by pentylenetetrazole in the rats
Results from Real-time polymerase chain reaction (RT-polymerase chain reaction (PCR)) analysis revealed a significant increase in the expression of NR1 mRNA in the pentylenetetrazole group, when
Summary
The flavone, 5, 6, 7-trihydroxyflavone, known as baicalein (Figure 1), is a natural isolate obtained from Scutellaria baicalensis Georgi. The protective effect of baicalein against pentylenetetrazole-induced chronic epilepsy in the rat was investigated. Changes in the behaviour of the experimental rats were analysed on the day following each treatment with baicalein, for the 30 days of the study. Half of the brain material from each animal was subjected to RT-PCR analysis. The animals were assigned randomly to 6 groups (5 rats/group): normal control, model and four treatment groups which were separately and intraperitoneally injected 20, 30, 40 and 50 mg/kg baicalein. The animal model of chronic epilepsy was prepared by intraperitoneal administration of 35 mg/kg pentylenetetrazole for 28 consecutive days. The paraffin-embedded hippocampal tissue sections were de-paraffinized in boiling xylene. The paraffin-embedded hippocampus tissue sections were subjected to de-paraffinization in boiling xylene, followed by re-hydration in ethyl alcohol gradient. Values of p < 0.05 were considered statistically significant
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