ABSTRACT
Acrylamide (ACR) is known to be a neurotoxic agent for humans and animals that has many applications in industry. Alpha-mangostin is a natural antioxidant that is extracted from mangosteen. This study aimed to investigate the protective effects of alpha-mangostin against ACR-induced neurotoxicity in rats and PC12 cells. Male Wistar rats were used in this investigation for 11 days, divided into 8 groups: 1. control group (normal saline), 2. ACR (50 mg/kg, i.p.), 3-6. ACR + alpha-mangostin (20, 40, 60 mg/kg, p.o.), 7. ACR + vitamin E (200 mg/kg, i.p., every other day) 8. alpha-mangostin (60 mg/kg, p.o.). On the last day of the study, the behavioral test was performed. The amounts of malondialdehyde (MDA) and glutathione (GSH) were measured. Also, the effects of ACR and alpha-mangostin were assessed by MTT assay on PC12 cells, and the levels of reactive oxygen species (ROS), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3 proteins were measured by Western blotting. Receiving ACR caused motor disorders in animals, increased MDA, and decreased GSH levels of the cerebral cortex versus the control group. Alpha-mangostin (60 mg/kg) reduced ACR motility disorders, MDA amounts, and augmented GSH levels. The concurrent administration of vitamin E and ACR reduced gait score, MDA level, and amplified GSH content versus the ACR group. In the in vitro section, alpha-mangostin (1.25 µM, 24 h) increased cell viability, attenuated ROS, Bax/Bcl-2, and cleaved caspase-3 levels versus the ACR group. Alpha-mangostin reduced the toxicity of ACR by inhibiting oxidative stress and apoptosis. Therefore, it could be a promising compound for managing ACR-induced neurotoxicity.