Salicylic acid protects against chronic L-DOPA-induced 6-OHDA generation in experimental model of parkinsonism.
The present study evaluated the ability of salicylic acid (SA) to attenuate long-term L-DOPA-induced 6-hydroxydopamine (6-OHDA) formation in the striatum of mice, and to protect against the resulting dopaminergic neurotoxicity. The production of 6-OHDA from dopamine in vitro from ferrous-ascorbate-dopamine (FAD) hydroxyl radical ((*)OH) generating system or in vivo in the striatum following prolonged administration of L-DOPA in mice were found to be significantly attenuated by SA. Intra-median forebrain bundle infusion of FAD, but not equivalent dose of ferrous ion or dopamine individually, caused significant striatal dopamine depletion, which was blocked by SA administration. The dose- and time-dependent increase in the formation of 6-OHDA following L-DOPA treatment in the mouse striatum was synergistically enhanced to the systemic administration of the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. SA treatment significantly attenuated the L-DOPA plus the parkinsonian neurotoxin-induced striatal 6-OHDA generation, and protected against striatal dopamine loss. The present study demonstrated a novel mode of dopaminergic neuroprotection by SA and its possible therapeutic implication in the treatment of Parkinson's disease.
Borah
Anupom
A
Division of Cell Biology and Physiology, Laboratory of Clinical & Experimental Neuroscience, Indian Institute of Chemical Biology CSIR, 4 Raja S C Mullick Road, Kolkata 700032, West Bengal, India.
Mohanakumar
Kochupurackal P
KP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000009:adverse effects*; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016627:Oxidopamine / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000494:pharmacology / Q000627:therapeutic use*
D015259:Dopamine Agents; D018696:Neuroprotective Agents; D012459:Salicylates; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid