Effect of carnosic acid on acrylamide induced neurotoxicity: in vivo and in vitro experiments

Abstract

Acrylamide (ACR), one of the most toxic chemical agents in humans and animals has several uses in different industries. Carnosic acid is an important biological antioxidant extracted from rosemary. In this study, the protective effect of carnosic acid on ACR-induced neurotoxicity in rat and PC12 cells has been investigated. Male Wistar rats were randomly divided into eight groups including (1) control group, (2) ACR (50 mg/kg, i.p.), (3-6) ACR plus carnosic acid (5, 10, 20, and 40 mg/kg, i.p.), (7) ACR plus vitamin E (200 mg/kg i.p., every other day), and (8) carnosic acid (40 mg/kg i.p.). After 11 days, behavioral tests were evaluated. Malondialdehyde (MDA), glutathione (GSH) and Bax, Bcl-2, and caspase 3 protein levels in brain tissue were measured. In in vitro study, the protective effects of carnosic acid on ACR toxicity were assessed by MTT assay. ACR caused severe motor impairment compared to control, increased MDA, and decreased GSH level. ACR increased Bax/Bcl-2 ratio and cleaved caspase-3. Carnosic acid (40 mg/kg) significantly recovered locomotor disorders. Additionally, carnosic acid increased GSH content, reduced MDA, and decreased Bax/Bcl-2 ratio, and caspase 3 protein levels. Carnosic acid increased cell viability compared to ACR at concentrations of 2.5-10 μM. Carnosic acid is the most abundant antioxidant compound found in the rosemary leaves. Recently, natural compounds have been suggested as potential treatment interventions for various diseases through their antioxidant properties. In this study, carnosic acid reduced ACR-induced toxicity through inhibition of oxidative stress and apoptosis.

Keywords: Acrylamide; PC12 cells; apoptosis; carnosic acid; neurotoxicity; oxidative stress.