Protective effect of L-carnitine against H(2)O(2)-induced neurotoxicity in neuroblastoma (SH-SY5Y) cells.

4-N-trimethylammonium-3-hydroxybutyric acid (L-carnitine) is an endogenous mitochondrial membrane compound and some studies have reported that L-carnitine could effectively protect various cells against oxidative injury both in vitro and in vivo. In the present study, we used the human neuroblastoma SH-SY5Y cell line as an in vitro model and assessed the effect of L-carnitine on hydrogen peroxide (H(2)O(2))-mediated oxidative stress and neurotoxicity. Cells in culture were treated with different concentrations of H(2)O(2) alone or pretreated with L-carnitine. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, transmission electron microscopy, agarose gel electrophoresis, biochemical methods, and Western blotting were employed in the present study. Pretreatment with L-carnitine for 3 hours inhibited H(2)O(2)-induced cell viability loss, morphological changes, intracellular reactive oxygen species generation, and lipid peroxidation in a concentration-dependent manner. Endogenous anti-oxidant defense components including total anti-oxidative capacity, glutathione peroxidase, catalase, and superoxide dismutase were also promoted by L-carnitine. Meanwhile, H(2)O(2)-induced down-regulation of Bcl-2, up-regulation of Bax, and DNA damage and apoptosis were also inhibited in the presence of L-carnitine. Taken together, these results suggest that L-carnitine may function as an anti-oxidant to inhibit H(2)O(2)-induced oxidative stress as well as regulation of Bcl-2 family and prevent the apoptotic death of neuronal cells, which might be beneficial for the treatment of oxidative stress in neurodegenerative diseases.