Mahboobeh Navabi - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Mahboobeh Ghasemzadeh Rahbardar - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Soghra Mehri - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Hossein Hosseinzadeh - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s): Acrylamide (ACR) induces neurotoxicity in humans and animals through different mechanisms. Sitagliptin is a type-۲ diabetes medication with neuroprotective properties. The effects of sitagliptin against neurotoxicity stimulated by ACR were examined.Materials and Methods: Male Wistar rats were classified as follows: ۱. Control (normal saline, ۱۱ days, IP), ۲. ACR (۵۰ mg/kg, ۱۱ days, IP), ۳. ACR (۱۱ days, days ۱۱-۲۰ normal saline), ۴-۷. ACR+sitagliptin (۵, ۱۰, ۲۰, and ۴۰ mg/kg, ۱۱ days, IP), ۸. ACR+sitagliptin (۱۰ mg/kg, days ۶-۱۱), ۹. ACR+sitagliptin (۱۰ mg/kg, days ۶-۲۰), ۱۰. Sitagliptin (۴۰ mg/kg, ۱۱ days), ۱۱. ACR+vitamin E (۲۰۰ mg/kg, IP). Finally, the gait score was evaluated. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured in cortex tissue.  Also, IL-۱β, TNF-α, and caspase-۳ levels were assessed in the cortex by western blotting. Results: ACR caused movement disorders, triggered oxidative stress, and raised TNF-α, IL-۱β, and caspase-۳ cleaved levels. Supplementation of sitagliptin (۱۰ mg/kg) along with ACR, in ۳ protocols, reduced gait disorders compared to the ACR group. Receiving sitagliptin in all doses plus ACR and injection of sitagliptin (۱۰ mg/kg) from days ۶ to۱۱ reduced the MDA level of cortex tissue. Sitagliptin (all doses) plus ACR increased the GSH level of the cortex tissue. Sitagliptin (۱۰ mg/kg) with ACR dropped the amounts of TNF-α and caspase-۳ cleaved proteins in cortex tissue but did not affect the IL-۱β level.Conclusion: Sitagliptin disclosed preventive and therapeutic effects on ACR neurotoxicity. Sitagliptin possesses antioxidant, anti-inflammatory, and anti-apoptotic properties and inhibits CR neurotoxicity in rats.

Anti-Oxidants, Caspases, Glutathione, Inflammation, Malondialdehyde, Neurotoxicity Syndromes, Tumor necrosis factors