Carvedilol attenuates acrylamide-induced brain damage through inhibition of oxidative, inflammatory, and apoptotic mediators

Document Type : Original Article

Authors

1 Department of Pharmacology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran

2 Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran

Abstract

Objective(s): Acrylamide is a potent neurotoxic compound and has harmful effects on brain cells. Acrylamide promotes oxidative, inflammatory, and apoptotic mediators in the CNS leading to neurological disorders. The goal of the current study was to examine the potential protective effect of carvedilol and its underlying mechanisms in a mouse model of acrylamide-induced brain injury. 
Materials and Methods: Mice were treated with acrylamide (50 mg/kg/day, IP) and carvedilol (5 and 10 mg/kg/day, oral) for 11 continuous days. At the end of the experiment, mice were subjected to gait assessment. They were sacrificed and brain tissues were collected for histological and biochemical analysis. 
Results: The results showed that treatment of mice with carvedilol decreased acrylamide-induced bodyweight loss, abnormal gait, and histopathological damage in the brain tissue. Carvedilol treatment significantly reduced the levels of malondialdehyde (MDA) and carbonyl protein and increased the levels of glutathione (GSH), catalase, superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Carvedilol treatment also decreased myeloperoxidase (MPO) activity, expression of nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), overproduction of nitric oxide (NO) and proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the brain of mice exposed to acrylamide. Furthermore, administration of carvedilol significantly decreased the levels of bax, cytochrome-c, and caspase-3 as markers of apoptosis in acrylamide-treated mice. 
Conclusion: These findings indicate that carvedilol is able to attenuate acrylamide-induced damage to the CNS by inhibition of oxidative stress, inflammation, and apoptosis. 

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 25, Issue 1
January 2022
Pages 60-67

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