Evaluation of Neuroprotective Role of Drugs That Modify Renin Angiotensin System on Histoanatomical Structures of Brain in Animal Models of Parkinson’s Disease

Abstract

Background and objectives Current parkinsonian treatments do not address the disease's aetiology or development. Routine drugs rarely affect issues of neuronal protection and endurance in dopaminergic neurons. With deeper understanding of brain renin-angiotensin system, many angiotensin converting enzyme inhibitors and angiotensin receptor blockers are evaluated for the management of parkinsonism. The main goal of this study was to evaluate and compare the anti-disease parkinson's properties of captopril, perindopril, losartan, and the standard anti parkinson's disease drugs (levodopa) in rotenone, MPTP, and paraquat induced models in wistar albino rats and swiss albino mice with the standard anti-disease parkinson's disease drugs (levodopa). The other objective was to evaluate and compare the neuroprotective role of captopril, perindopril and losartan on histoanatomical structures of brain in rotenone, MPTP and paraquat induced parkinson‘s disease animal models in wistar albino rats and swiss albino mice. Methodology: Healthy adult wistar albino rats of either sex weighing 180-250gm were selected and divided into six groups, each containing six animals in rotenone model. Similarly, healthy adult swiss albino mice of either sex weighing 20-30gm of six groups, each containing six animals were selected for MPTP and paraquat models separately. All the rodents were obtained from the animal house; Institutional Animal Ethical Committee approved before the start of the study. Effects of captopril (20 mg/kg), perindopril (5 mg/kg) and losartan (90 mg/kg) were evaluated in rotenone, MPTP and paraquat models. Neurobehavioral effects were noted through spontaneous locomotor activity, rotarod test, hole board test, forced swim test, tail suspension test and elevated plus maze test. After documenting the neurobehavioral parameters the rodents were anaesthetized and sacrificed, the brain tissue was extracted by dissection method. Oxidative stress markers, neurotransmitters and inflammatory marker were evaluated in one hemisection. Other hemisection was H & E stained for analysing histoanatomical changes, and Bcl-2 immunohistochemistry study was done to evaluate the anti-apoptotic effects of these drugs. Results Perindopril and losartan partially improved motor functions in rotenone, MPTP and paraquat models. All the drugs had shown anti-depressant action in all the three models. Perindopril and losartan had shown anti-anxiety action. Captopril, perindopril and losartan had exhibited neuroprotective role as evidenced by the decreased glutamate levels in all the three models. Captopril, perindopril and losartan had documented the neuroprotective role as evidenced by improved oxidative stress marker levels in all the three models. Captopril, perindopril and losartan had proved greater neuroprotective role as evidenced by the increased serotonin, dopamine and acetylcholine levels in rotenone and MPTP models. Captopril, perindopril and losartan had not resulted in any significant histoanatomical changes in the hippocampus, prefrontal cortex, corpus striatum and hypothalamus sections as H&E sections, and shown near normal histoanatomy. Captopril and perindopril had shown significant anti-apoptotic property as evidenced through Bcl-2 immunohistoreactivity in rotenone and paraquat model respectivelyConclusion Overall, captopril, perindopril and losartan had significantly improved the non-motor behavioural aspects of PD. All the three drugs significantly decrease the oxidative stress levels inferring that, they are neuroprotective in all the three models.