O-EP004. Targeting epilepsy with novel therapeutic entities to investigate the biochemical and molecular mechanisms

Abstract

Introduction . Analysis of anticonvulsant action of novel therapeutic entity (NTE) in kindling (Pentylenetetrazole (PTZ)) and acute (Kainic Acid (KA)) seizure mice (male swiss albino) models. Methods . The NTE (NP-VM1) was screened from a class of 5 hydrazone derivatives of 2,4-disubstituted thiazole through subcutaneous PTZ and neurotoxicity screening followed by log-probit analysis for determining ED50, TD50 and protective-index (PI). Neuroprotective potential of the NTE was analyzed in both models and was validated through behavioral screening tests and oxidative stress estimation (MDA, GPx and SOD levels). Results were analyzed by ANOVA single factor and Tukey’s post-hoc test. Results . NP-VM1 showed significant biological activity in screening. It significantly reduced the seizure activity in both models. Significant increase in the spatial learning ability in Morris Water Maze test was further confirmed by increased recognition index in Object Recognition Test. Reduced transfer latency and time spent in open arm in Elevated Plus Maze test along with increased rearings and movement through the centre in Open Field Test signified restoration of behavior normalcy and locomotion ability. Rotarod test showed that NTE significantly negated the neurotoxic and ataxic effects which was further proved by enhanced GPx and SOD levels and attenuated MDA levels in the hippocampus. The results of sucrose consumption test were however not statistically significant. Conclusion . NP-VM1 significantly augmented the ROS detoxification thereby fortifying the neurons from chronic damage, which was evident by the restoration of behavioral normalcy and learning, motor coordination and locomotion abilities.