Title : To evaluate the effect of endothelin receptor agonist IRL-1620 alone and in combination with donepezil in modulating neurodegeneration produced by amyloid-? in rats
IRL-1620 is a chemical entity that have neuroprotective activity as it increases growth factors VEGF and NGF. The Present study hypothesis is to evaluate the effect of IRL-1620 on Aß induced memory loss in the rat model of Alzheimer’s disease. We have taken 58 males adult Wistar rats (200-250gm) for our study and they were divided in 5 experimental group. There are three more experimental group on which Dose ranging study was performed. Animals were treated with ICV injection 10µl(5µl bilaterally) of Aß1-42 or PBS (sham operated group).The treatment of IRL-1620 was given on day 8th from day 0.On 21 day final evaluation of all neurobehavioraltest (spatial memory and short term memory) was done in all groups. Other tests for e.g. Biochemical evaluation and Molecular parameter were also evaluated for the efficacy of IRL-1620.IRL-1620 (5µg/kgi.v.) alone and in combination with Donepezil(1mg/kg orally) showed Signiant improvement of memory in compareign with Sham and Aß group (p<0.05). The escape latency and mean time spent in target quadrant was found to be increased significantly in case of the IRL-1620 (5µg/kg i.v.) alone and in combination with Donepezil (1mg/kg orally) as compare to IRL-1620 (7µg/kg i.v.) and IRL-1620 (9µg/kg i.v.). Short term memory is also improved by IRL-1620 (5µg/kg i.v.) which was significant in compareign with control, IRL-1620(7µg/kg i.v.) and 1RL-1620 (9µg/kg).There is also improvement in memory by GCSF (5µg/kg i.v.) oxidative stress parameter by IRL-1620(5µg/kg i.v.)and in combination with Donepezil(1mg/kg orally) found to be improved.e.g. reduction in lipid peroxidation, acetylcholinesterase levels and increase in antioxidant enzyme level.At molecular level and IHC shown that IRL-1620(5µg/kg i.v.) and in combination with Donepezil(1mg/kg orally) have shown improved expression level of VEGF,NGF and ET-B as compare to IRL-1620 (7µg/kg i.v.) and 1RL-1620 (9µg/kg). Histopathological and analysis has shown This study finding demonstrated that there is improvement in memory and neurobehavioral parameters with IRL-1620 treatment alone (5µg/kg) and along Donepezil in Alzheimer’s disease model of rats.