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Pharmacological Screening of Nsaid’s For Their Probable Central Nervous System Effect and Their Role in Neurodegenerative Diseases

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dc.contributor.author Naeem, Sadaf.
dc.date.accessioned 2019-01-14T05:48:37Z
dc.date.accessioned 2020-04-11T15:11:52Z
dc.date.available 2020-04-11T15:11:52Z
dc.date.issued 2015
dc.identifier.govdoc 16902
dc.identifier.uri http://142.54.178.187:9060/xmlui/handle/123456789/4422
dc.description.abstract Inducible cyclo-oxygenase (COX) expression in the brain is associated with acute neurotoxicity, such as seizures and ischemia. On the other hand COX 1 and 2 both are related to delayed pro-inflammatory activities, which are ought to exacerbate the neuronal damage in neurodegenerative diseases. It was postulated in last decade that non steroidal anti-inflammatory drugs (NSAIDs) which are widely used in clinical situation as anti-inflammatory, analgesics and antipyretic drugs by inhibiting COX pathway in brain can prevent neurodegeneration. However it is still unknown whether NSAIDs have effect on the development on the central nervous system and play a major role to prevent and treat neurodegenerative disease. Previous clinical, epidemiological and experimental data revealed that repeated and long term use of NSAIDs prevent neurodegeneration by inhibiting brain COX isoenzymes and recommended as a new emerging approach. In the present study we aimed to evaluate the effect of diclofenac, ibuprofen and celecoxib on behavioral and biochemical parameters as well as disease severity assessment not only in parkinson’s patients but on chlorpromazine induced parkinson rat model. A single blind clinical study was conducted in four groups of 40 parkinson’s patients. The cognition was measured by MMSE and MoCA test, depression assessed by HDRS test, daily living functioning judged with ADCS-ADL scale and disease severity by Hoehn & Yahr staging and descriptive UPDRS scale. The outcomes were better among patients treated with NSAIDs than control patients. NSAIDs treated patients showed significant improvement in MMSE, MoCA and ADCS-ADL scores after 2 month treatment period from baseline score. However insignificant results were also observed after 2 month treatment with respect to depression and disease severity. The most frequent adverse events during 2 month treatment period were nausea, dyspepsia, elevated hepatic enzymes, and hypertension. NSAIDs showed significant increased SGOT, SGPT, and bilirubin levels but no significant change in GGT and alkaline phosphatase after 2 month treatment was noted. NSAIDs showed significant increased levels of urea and creatinin after 2 month. We found elevated Cortisol levels at baseline in all parkinson patients after taking NSAID we observed slightly reduced levels of cortisol from baseline as compare to control patients but results were insignificant. Behavioral and histopathological examination of NSAIDs treated rats after chlorpromazine induced parkinsonism was observed. NSAIDs were administered after 30 minutes of 3mg/kg ip injection of chlorpromazine up to 21 day. After 21 day we observed significant motor impairment in CPZ treated rat in open field, catalepsy and wire hanging test while NSAIDs treated rat showed significant improvement comparable to standard L-dopa/carbidopa group. NSAIDs treated rats showed significant improved cognitive behaviors in radial arm maze, water maze and passive avoidance test as compare to control and CPZ group. Depression was marked with CPZ group on forced swimming induced test and cage crossing test while NSAIDs treatment improved depression after 21 days. NSAIDs treated rats slightly reduced their weight after 21 days as compare to control and CPZ group while CPZ group significantly increased body weight. Anxiety was assessed by using elevated plus maze. NSAIDs showed anxiety like behavior after 21 day treatment but CPZ treated rats showed anxiolytic effect. Histopathological examination of brain tissue of NSAIDs treated group revealed minimal neuronal destruction and gliosis as compare to CPZ group. In conclusion results of this clinical and experimental study explain that NSAIDs treatment show moderate improvement in parkinson associated cognitive decline, motor impairment and in their daily life function. Adverse drug events were also observed, hence prolong use can only be recommended after extensive study. en_US
dc.description.sponsorship Higher Education Commission of Pakistan, Pakistan en_US
dc.language.iso en_US en_US
dc.publisher University of Karachi, Karachi en_US
dc.subject Pharmacological Screening of Nsaid’s For Their Probable Central Nervous System Effect and Their Role in Neurodegenerative Diseases en_US
dc.title Pharmacological Screening of Nsaid’s For Their Probable Central Nervous System Effect and Their Role in Neurodegenerative Diseases en_US
dc.type Thesis en_US


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