Inhibitory effect of melatonin on homocysteine-induced lipid peroxidation in rat brain homogenates.
Oxidative damage is implicated in several pathologies including cardiovascular disease. As a model system to study the response of cells to oxidative insults, homocysteine toxicity was examined since it is an independent risk factor for atherosclerotic disease. The levels of malondialdehyde and 4-hydroxyalkenals were assayed as an index of oxidatively damaged lipid. In in vitro experiments, the increase of lipid peroxidation products induced by homocysteine were concentration- and time-dependent. To study the protective effect of melatonin on homocystine induced lipid peroxidation, brain homogenates were treated with different concentrations of melatonin. The accumulation of malondialdehyde and 4-hydroxyalkenals induced by homocysteine was significantly reduced by melatonin in a concentration-dependent manner. Additionally, a melatonin concentration of 1.5 mM reduced the levels of oxidatively damaged lipid products below those measured in control homogenates (no homocysteine, no melatonin). These data suggest that melatonin, an endogenous antioxidant may have a role in protecting cells from oxidative damage due to homocysteine and they support the idea that pharmacological concentrations could be used as a therapeutic agent in reducing cardiovascular disease where homocysteine may be a causative or contributing agent.
Osuna
Carmen
C
Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio 78229-3900, USA.
Reiter
Russel J
RJ
García
Joaquin J
JJ
Karbownik
Malgorzata
M
Tan
Dun Xian
DX
Calvo
Juan R
JR
Manchester
Lucien C
LC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006710:Homocysteine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D006710:Homocysteine; D008550:Melatonin