Investigating the effect of telmisartan on acrylamide-induced neurotoxicity through in vitro and in vivo methods

Objective(s):  Acrylamide (ACR) is an environmental contaminant and neurotoxin. Telmisartan is an AT۱ blocker that has neuroprotective properties basically through its anti-oxidant effect. The effect of telmisartan on ACR-induced neurotoxicity was investigated in this study. Materials and Methods: Male Wistar rats were randomly assigned to eight groups (n=۶): ۱:Control (normal saline), ۲:ACR (۵۰ mg/kg, ۱۱ days, IP), ۳:ACR+vitamin E (۲۰۰ mg/kg, every other day, ۱۱ days), ۴-۶:ACR+telmisartan (۰.۶, ۱.۲۵, and ۲.۵ mg/kg, ۱۱ days, IP), ۷:ACR+telmisartan (۰.۶ mg/kg, days ۳–۱۱), ۸:Telmisartan (۲.۵ mg/kg, ۱۱ days). The behavioral test and blood pressure were assessed after ۱۱ days. Then, the levels of MDA and GSH in brain tissue were measured. The MTT assay was used to evaluate the effect of telmisartan on ACR-induced cytotoxicity.Results: Exposing PC۱۲ cells to ACR decreased cell viability versus the control group. Pretreating PC۱۲ cells with telmisartan (۰.۰۱۲۵, ۰.۰۲۵ µM) enhanced cell viability compared with the ACR group. Compared with control samples, ACR significantly caused motor impairment, elevated MDA, and reduced GSH levels. Locomotor abnormalities were significantly ameliorated by telmisartan (۰.۶, ۱.۲۵ mg/kg, ۱۱ days) and vitamin E versus the ACR group. Receiving telmisartan (۰.۶, ۱.۲۵, and ۲.۵ mg/kg) and vitamin E along with ACR decreased MDA levels and enhanced GSH content compared with the ACR group.  There was no significant difference in animal blood pressure between the groups.Conclusion: Oxidative stress has a chief role in the neurotoxicity of ACR. Telmisartan (in doses that do not affect blood pressure) ameliorated ACR-induced toxicity by inhibiting oxidative stress.

Keywords:

Anti-Oxidants , Cell Survival , Motor disorders , Neurotoxins , PC۱۲ cells , Vitamin E