Indomethacin reduces lipid peroxidation in rat brain homogenate by binding Fe2+.
One of the hallmarks of Alzheimer's disease (AD) is the progressive degeneration of cholinergic neurons in the cerebral cortex and hippocampus. It is generally accepted that this neuronal degeneration is due to free-radical-induced damage. These free radicals attack vital structural components of the neurons. This implies that agents that reduce free radical generation could potentially delay the progression of AD. Free radical generation in the brain is assisted by the presence of iron, required by the Fenton reaction. Thus, agents that reduce iron availability for this reaction could potentially reduce free radical formation. Since non steroidal anti-inflammatory drugs (NSAIDS) have been shown to reduce the severity of AD, we investigated the possible mechanism by which indomethacin could afford neuroprotection. Our results show that indomethacin (1 mM) is able to reduce the iron-induced rise in lipid peroxidation in rat brain homogenates. In addition, our NMR data indicate that indomethacin binds the Fe(2+)/Fe(3+) ion. This was confirmed by a study using UV/Vis spectrophotometry. The results imply that indomethacin provides a neuroprotective effect by binding to iron and thus making it unavailable for free radical production.
Anoopkumar-Dukie
Shailendra
S
Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.
Lack
Barbara
B
McPhail
Kerry
K
Nyokong
Tebello
T
Lambat
Zaynab
Z
Maharaj
Deepa
D
Daya
Santy
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D007213:Indomethacin / Q000378:metabolism* / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D007501:Iron; D007213:Indomethacin