Alpha-mangostin Protects PC12 Cells Against Neurotoxicity Induced by Cadmium and Arsenic

Arsenic and cadmium are nonessential elements that are of importance in public health due to their high toxicity. Contact with these toxic elements, even in very small amounts, can induce various side effects, including neurotoxicity. Oxidative stress and apoptosis are part of the main mechanisms of arsenic- and cadmium-induced toxicity. Alpha-mangostin is the main xanthone derived from mangosteen, Garcinia mangostana, with anti-oxidative properties.In this study, PC12 cells were selected as a nerve cell model, and the protective effects of alpha-mangostin against neurotoxicity induced by arsenic and cadmium were investigated. PC12 cells were exposed to cadmium (5-80 µM) and arsenic (2.5-180 µM) for 24 h. Cytotoxicity, reactive oxygen species (ROS) production, and the protein expression of Bax, Bcl2, and cleaved caspase 3 were determined using MTT assay, fluorimetry, and western blot, respectively.Arsenic (10-180 µM) and cadmium (50-80 µM) significantly reduced cell viability. IC₅₀ values were 10.3 ± 1.09 and 45 ± 4.63 µM, respectively. Significant increases in ROS, Bax/Bcl-2 ratio, and cleaved caspase-3 were observed after arsenic and cadmium exposures. Cell viability increased and ROS production decreased when cells were pretreated with alpha-mangostin for 2 h. Alpha-mangostin reduced the increased level of cleaved caspase-3 induced by cadmium and decreased the elevated level of the Bax/Bcl-2 ratio after arsenic exposure.Alpha-mangostin significantly increased cell viability and reduced oxidative stress caused by cadmium and arsenic in PC12 cells. Moreover, alpha-mangostin reduced cadmium-induced apoptosis through the reduction in the level of cleaved caspase 3. Further studies are required to determine the different mechanisms of alpha-mangostin against neurotoxicity induced by these elements.