Attenuation of acrylamide-induced neurotoxicity by supplementation of sitagliptin in Wistar rats

Document Type : Original Article

Authors

1 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Acrylamide (ACR) induces neurotoxicity in humans and animals through different mechanisms. Sitagliptin is a type-2 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: 1. Control (normal saline, 11 days, IP), 2. ACR (50 mg/kg, 11 days, IP), 3. ACR (11 days, days 11-20 normal saline), 4-7. ACR+sitagliptin (5, 10, 20, and 40 mg/kg, 11 days, IP), 8. ACR+sitagliptin (10 mg/kg, days 6-11), 9. ACR+sitagliptin (10 mg/kg, days 6-20), 10. Sitagliptin (40 mg/kg, 11 days), 11. ACR+vitamin E (200 mg/kg, IP). Finally, the gait score was evaluated. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured in cortex tissue.  Also, IL-1β, TNF-α, and caspase-3 levels were assessed in the cortex by western blotting. 
Results: ACR caused movement disorders, triggered oxidative stress, and raised TNF-α, IL-1β, and caspase-3 cleaved levels. Supplementation of sitagliptin (10 mg/kg) along with ACR, in 3 protocols, reduced gait disorders compared to the ACR group. Receiving sitagliptin in all doses plus ACR and injection of sitagliptin (10 mg/kg) from days 6 to11 reduced the MDA level of cortex tissue. Sitagliptin (all doses) plus ACR increased the GSH level of the cortex tissue. Sitagliptin (10 mg/kg) with ACR dropped the amounts of TNF-α and caspase-3 cleaved proteins in cortex tissue but did not affect the IL-1β 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. 

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 27, Issue 3
March 2024
Pages 311-318

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