Protective effect of aspirin and gentisic acid, a plant-derived phenolic acid, on acrylamide-induced neurotoxicity by inhibiting apoptosis and autophagy.

Acrylamide (ACR) is a toxic agent for humans and animals. Gentisic acid, an aspirin metabolite, has antioxidant activity. Therefore, the present study investigated the probable protective effects of aspirin and gentisic acid on ACR-induced neurotoxicity in PC12 cells and rats. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the effects of aspirin and gentisic acid (1.25, 2.5, 5 µM) on ACR (5 mM) toxicity. Male Wistar rats were randomly divided into 13 groups: (1) Control group, (2) ACR (50 mg/kg, 11 days, i.p.), (3-5) ACR + aspirin (25, 50, 75 mg/kg, 11 days, p.o.), (6-8) ACR + gentisic acid (25, 50, 75 mg/kg, 11 days, p.o.), (9) ACR + vitamin E (200 mg/kg, every other day, i.p.), (10, 11) Aspirin (75, 100 mg/kg, 11 days, p.o.), (12, 13) Gentisic acid (75, 100 mg/kg, 11 days, p.o.). Behavioral tests were assessed on the final day of the study. In the cerebral cortex, malondialdehyde (MDA), glutathione (GSH), cleaved-caspase-3, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein levels were evaluated. When compared with the ACR group, aspirin (2.5, 5 µM) and gentisic acid (2.5 µM) significantly enhanced cell viability. In comparison to the control group, ACR induced severe motor impairment, elevated MDA, cleaved-caspase-3, LC3 II/I ratio, and decreased GSH levels in the cerebral cortex of rats. ACR-induced changes were significantly reversed by aspirin and gentisic acid (25 mg/kg). Oxidative stress, apoptosis, and autophagy play important roles in the neurotoxicity of ACR. Aspirin and gentisic acid significantly reduced ACR-induced toxicity by inhibiting the mentioned mechanisms.