Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 94, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2021.107431
Keywords
Parkinson?s disease; Rotenone; Paracetamol; Cannabinoid receptors; Neurodegenerative diseases
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The study demonstrated the neuroprotective effects of paracetamol (PCM) against rotenone-induced Parkinson's disease (PD) symptoms. PCM alleviated motor impairments, prevented weight loss, restored tissue structure, and reversed reduction in dopamine content. Additionally, PCM exhibited antioxidant, anti-inflammatory, anti-apoptotic activities, and modulated cannabinoid receptors to protect against PD.
Parkinson?s disease (PD) is a disabling progressive neurodegenerative disease. So far, PD?s treatment remains symptomatic with no curative effects. Aside from its blatant analgesic and antipyretic efficacy, recent studies highlighted the endowed neuroprotective potentials of paracetamol (PCM). To this end: the present study investigated: (1) Possible protective role of PCM against rotenone-induced PD-like neurotoxicity in rats, and (2) the mechanisms underlying its neuroprotective actions including cannabinoid receptors? modulation. A doseresponse study was conducted using three doses of PCM (25, 50, and 100 mg/kg/day, i.p.) and their effects on body weight changes, spontaneous locomotor activity, rotarod test, tyrosine hydroxylase (TH) and ?-synuclein expression, and striatal dopamine (DA) content were evaluated. Results revealed that PCM (100 mg/kg/day, i.p.) halted PD motor impairment, prevented rotenone-induced weight loss, restored normal histological tissue structure, reversed rotenone-induced reduction in TH expression and striatal DA content, and markedly decreased midbrain and striatal ?-synuclein expression in rotenone-treated rats. Accordingly, PCM (100 mg/kg/ day, i.p.) was selected for further mechanistic investigations, where it ameliorated rotenone-induced oxidative stress, neuro-inflammation, apoptosis, and disturbed cannabinoid receptors? expression. In conclusion, our findings imply a multi-target neuroprotective effect of PCM in PD which could be attributed to its antioxidant, anti-inflammatory and anti-apoptotic activities, in addition to cannabinoid receptors? modulation.
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