Melatonin, the main secretory product of the pineal gland, has been shown to be potentially effective in prevention of numerous types of
neurodegenerative disorders in which
free radical processes are involved.
Homocysteine (Hcy), an independent risk factor for
atherosclerosis, undergoes auto-oxidation and generates
reactive oxygen species. The purpose of this study was to test whether intracerebroventricular (ICV) injection of Hcy leads to neural lipid peroxidation and also to investigate the protective effects of
melatonin on the brain tissue from oxidative stress of Hcy. Adult male Wistar rats under anaesthesia were injected ICV with Hcy at a dose of 143 microg/kg.
Melatonin was administered intraperitoneally to a group of rats for three consecutive days before Hcy injection. The rats were decapitated and brain tissues were removed and hippocampus, cortex and cerebellum were dissected. There was a significant development of oxidative stress as indicated by an increase in
malondialdehyde in hippocampus, cortex and cerebellum of rats injected with Hcy, whereas
melatonin prevented the elevation of lipid peroxidation. Furthermore,
melatonin significantly increased
glutathione levels and
glutathione peroxidase activity in all brain regions. The present study demonstrates that Hcy, in high levels, may be a causal factor in generation of
free radicals in the brain and it may be one of the mechanisms which cause neurodegeneration in elderly people. It also shows that
melatonin could potentially be beneficial in prevention of neurodegeneration caused by
hyperhomocysteinemia.