Pharmacological but not physiological concentrations of melatonin reduce iron-induced neuronal death in rat cerebral cortex.
Iron-mediated oxidative stress occurs in a wide variety of neurological disorders. The present study has investigated whether melatonin can alter the proportion of neurons that die in the 24 h period following 1.0 microl intracortical injections of 1.0 mM ferric ammonium citrate (FAC) or 0.9% saline. Rats which received systemic infusions of melatonin (5 mg/kg body weight per day) displayed a 40% reduction (P = 0.019) in the proportion of neurons killed by FAC. By contrast, reduction of endogenous melatonin by continuous light exposure did not significantly affect the extent of neuronal death. Furthermore, elevated or reduced melatonin levels did not alter the number of neurons killed by saline injections. We conclude that pharmacological concentrations of melatonin protect neurons against iron-induced injury.
Hayter
Catherine L
CL
School of Psychology, Psychiatry and Psychological Medicine, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
Bishop
Glenda M
GM
Robinson
Stephen R
SR
D000818:Animals; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects*; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005290:Ferric Compounds / Q000633:toxicity*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008550:Melatonin / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009930:Organic Chemicals; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D005290:Ferric Compounds; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; D000644:Quaternary Ammonium Compounds; C435731:fluoro jade; D008550:Melatonin; C013531:ferric ammonium citrate