title: Anti-inflammatory properties rather than anti-oxidant capability is the major mechanism of neuroprotection by sodium salicylate in a chronic rotenone model of Parkinson's disease.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder manifesting in motor, cognitive and behavioral anomalies. Loss of dopaminergic neurons in the substantia nigra region of the brain is the hallmark feature of PD, which is attributed to oxidative and inflammatory stress besides other diverse factors and hence drugs targeting these pathways hold promise as neuro-therapeutics. The anti-oxidative as well as anti-inflammatory properties of sodium salicylate (SS), suggest its neuroprotective potentials in PD. Since PD is a progressive neurodegenerative disorder, the mechanistic basis for utilizing SS as a neuroprotectant in PD could be better understood in the chronic models. The present study utilizes a rotenone-based model of PD to evaluate the neuro-modulatory efficacy of SS. Subcutaneous injection of rotenone (2mg/kg body weight) was given to male SD rats every day, for a period of 5 weeks, which developed all the essential features of PD in these animals. Simultaneously, another group was injected SS intraperitoneally at the dose of 100mg/kg body weight, in addition to the rotenone. In the animals receiving rotenone+SS, significant improvement was observed in the various characteristic hallmarks of PD such as dopamine and tyrosine hydroxylase levels as well as the motor dysfunction symptoms. It attenuated the reactive oxygen species levels significantly but failed to reduce the levels of protein carbonylation and lipid peroxidation. However, SS effectively abridged the levels of inflammatory mediators like cyclooxygenase-2 (COX-2), nuclear factor kappa B and inducible nitric oxide synthase. Correspondingly, a significant decrease in the levels of pro-inflammatory cytokines interleukin-6, interleukin-1β and tumor necrosis factor-α was also observed following SS co-treatment. Thus, neuroprotective efficacy of SS in this chronic model of PD can be largely attributed to its anti-inflammatory effects rather than its free radical-scavenging properties.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India. poonamthkur@gmail.com
authors.forename: P
authors.initials: P
authors.lastname: Thakur
authors.forename: B
authors.initials: B
authors.lastname: Nehru
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone; D012980:Sodium Salicylate / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012402:Rotenone; D015102:3,4-Dihydroxyphenylacetic Acid; D002374:Catalase; D008995:Monoamine Oxidase; D004298:Dopamine; D012980:Sodium Salicylate; D006719:Homovanillic Acid