In vivo and in vitro effects of crocetin and its amide derivative on acrylamide-induced neurotoxicity

Objective: Acrylamide (ACR) is a neurotoxic agent whose damage could be attenuated by antioxidants administration. Crocetin is a saffron-derived antioxidant that has neuroprotective effects. This study evaluates the protective effects of trans-sodium crocetinate (TSC) and its water-soluble derivative, Bis-N-(N-methylpyprazinyl) crocetinate (BMPC) against ACR neurotoxicity.Materials and Methods: PC۱۲ cells were treated with TSC and BMPC (۱.۹۵, ۳.۹, ۷.۸۱, ۱۵.۶۲, ۳۱.۲۵, ۶۲.۵, ۱۲۵, ۲۵۰, ۵۰۰, and ۱۰۰۰ μM) for ۲۴ hr. ACR was then added at a concentration of ۶.۵ mM (IC۵۰), and cell viability was assessed by ۳-(۴,۵-dimethylthiazol-۲-yl)-۲,۵-diphenyltetrazolium bromide. In the in vivo study, male Wistar rats were treated with ACR (۵۰ mg/kg, intraperitoneal (i.p.)) for ۱۱ days alone or in combination with TSC and BMPC (۲.۵, ۵, and ۱۰ mg/kg, i.p.) or vitamin E (۲۰۰ IU/kg, i.p.). Motor impairments were then evaluated. The cerebral cortex of sacrificed rats was taken for the malondialdehyde (MDA) and glutathione (GSH) levels measurement. Results: In vitro studies showed that TSC at a concentration of ۷.۸۱ μM and BMPC at concentrations of ۳.۹, ۷.۸۱, and ۱۵.۶۲ μM exhibited the lowest toxicity in acrylamide administration. In the in vivo study, pretreatment with ۲.۵, ۵, and ۱۰ mg/kg of TSC ameliorated behavioral impairments, but BMPC could not attenuate them. GSH and MDA were improved by ۲.۵, ۵, and ۱۰ mg/kg TSC and ۲.۵ mg/kg BMPC.Conclusion: TSC and BMPC administration improved behavioral index and oxidative stress injuries in Wistar rats exposed to ACR through MDA reduction and GSH content enhancement in the cerebral cortex.

Keywords:

Neurotoxicity , Trans-sodium crocetinate , Bis-N-(N-methylpyprazinyl) crocetinate , Acrylamide , Saffron , Oxidative stress