Study on potential protective effect of acetaminophen in experimentally induced parkinson's disease in rats

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease, following Alzheimer’s disease. Clinically, the disease is mainly characterized by motor impairments including: resting tremors, muscle rigidity, and aberrant gait, and posture. PD is characterized by two main pathological hall marks: 1) the progressive degeneration of the dopaminergic neurons originating from the substantia nigra pars compacta (SNpc) resulting in the depletion of dopamine (DA) output to the striatum, and 2) the accumulation of intra-neuronal proteinaceous inclusion called Lewy bodies (LB) containing -synuclein as the main component. Although the pathogenesis of PD is not yet clear, it is thought to involve several factors including: inflammatory processes, oxidative stress and apoptosis. Rotenone is a natural pesticide that can induce PD-like symptoms in rats. The chronic dosing of small doses of rotenone to rats is found to induce both motor features of PD. Acetaminophen (ACM) is a widely-used analgesic and anti-pyretic. During the past two decades, several researches demonstrated the potential of other uses of this drug including neuroprotective and anxiolytic action. Furthermore in 2005, ACM was proven to undergo a two-step metabolism, where it is first deacetylated in the liver to give the intermediate 4-aminophenol. This is followed by its conjugation with arachidonic acid in the brain, through the action of fatty acid amide hydrolase enzyme (FAAH), to form the active metabolite, AM404. AM404 was found to modulate the endocannabinoid system (ECB). Following researches tried to investigate whether the actions of ACM were due to this metabolite. It was reported that the analgesic and anxiolytic activity of ACM is dependent upon its