Establishing the probable mechanism of L-DOPA in Alzheimer's disease management.
Clinical data suggest the role of L-DOPA in Alzheimer's Disease (AD) though its mechanism of action in AD is not clear. Previous results suggest that L-DOPA might have a complex mixture of pro- and antioxidant effects contributing to tissue damage due to oxidative stress. Furthermore, entacapone, a COMT inhibitor, is known to retain greater levodopa levels in plasma during coadministration. Hence, the role of L-DOPA + entacapone in aluminum induced oxidative stress in the rat brain was evaluated. Sprague Dawley rats (n = 6/group) were treated with either the vehicle, aluminum, L-DOPA + entacapone or aluminum + L-DOPA + entacapone for 28 days. The intact brains were processed for lipid peroxidation (LPO) and superoxide dismutase (SOD) activity. Aluminum treatment showed highly elevated levels of LPO while the combination of L-DOPA and entacapone could not control this oxidative burst in the rat brains both in presence and absence of aluminum. No change was observed in the brain or the circulating SOD activity. Hence, it is derived that protective role of L-DOPA in AD management is not exerted through its antioxidant property and may be manifested due to its involvement in other pathways.
Nivsarkar
Manish
M
Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, SG Road, Thaltej, Ahmedabad-54, India. manishnivsarkar@yahoo.com
Banerjee
Aryamitra
A
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D002712:Chlorides / Q000633:toxicity; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007980:Levodopa / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D017607:Aluminum Compounds; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D002712:Chlorides; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D009570:Nitriles; D000077410:Aluminum Chloride; D007980:Levodopa; C071192:entacapone; D013482:Superoxide Dismutase