Melatonin protects SHSY5Y neuroblastoma cells from cobalt-induced oxidative stress, neurotoxicity and increased beta-amyloid secretion

Heavy metals are increasingly being implicated as causative agents in neuro degenerative diseases such as Alzheimer's disease (AD). Cobalt, a positivel y charged transition metal, has previously been shown to be in elevated lev els in the brain of AD patients compared with age-matched controls. In this study, we investigate the effects of cobalt as an inducer of oxidative str ess/cell cytotoxicity and the resultant metabolic implications for neural c ells. We show that cobalt is able to induce cell cytotoxicity (reduced MTT metabolism) and oxidative stress (reduced cellular glutathione). The pre-tr eatment of cells with the pineal indoleamine melatonin, prevented cell cyto toxicity and the induction of oxidative stress. Cobalt treatment of SHSY5Y cells increased the release of beta -amyloid (A beta) compared with untreat ed controls (ratio A beta 40/42). Melatonin pre-treatment reversed the dele terious effects of cobalt. These findings are significant as cobalt is an e ssential nutritional requirement, usually bound to cobalamin (vitamin B-12) , for all animals which in the unbound form could lead to neurotoxicity.