6-Hydroxymelatonin protects against cyanide induced oxidative stress in rat brain homogenates.
Both 6-hydroxymelatonin and N-acetyl-N-formyl-5-methoxykynurenamine are photodegradants and enzymatic metabolites of melatonin and are known to retain equipotent activity against potassium cyanide-induced superoxide generation compared to melatonin. It is not clear whether one or both of these metabolites is responsible for this effect. The present study therefore investigates the possible manner in which 6-hydroxymelatonin protects against oxidative stress induced by cyanide in rat brain homogenates. We examined the ability of 6-hydroxymelatonin to scavenge KCN-induced superoxide anion generation as well as lipid peroxidation. In addition, we also examined the effect of this indole on lactate dehydrogenase activity (LDH) as well as mitochondrial electron transport using dichlorophenol-indophenol as an electron acceptor. The results of this study show that 6-hydroxymelatonin significantly reduces KCN-induced superoxide anion generation, which is accompanied by a commensurate reduction in lipid peroxidation. Partial reversal of the KCN-induced reduction in mitochondrial electron transport is accompanied by a similar reversal of mitochondrial LDH activity blunted by KCN. It can thus be proposed that 6-hydroxymelatonin is potentially neuroprotective against KCN-induced neurotoxicity.
Faculty of Pharmacy, Division of Pharmacology and Pharmaceutics, Rhodes University, 6140 Grahamstown, South Africa.
Deepa S
DS
Maharaj
Roderick B
RB
Walker
Beverley D
BD
Glass
Santy
S
Daya
D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003486:Cyanides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009580:Nitroblue Tetrazolium; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet
D003486:Cyanides; D005609:Free Radicals; D007202:Indicators and Reagents; D009580:Nitroblue Tetrazolium; D007770:L-Lactate Dehydrogenase; D008550:Melatonin; C012365:6-hydroxymelatonin