Sepideh beigmohammad ziarani,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: Acrylamide is responsible for developmental genotoxicity, neurotoxicity, and potentially carcinogenicity, of which neurotoxicity has been confirmed via human and animal experiments. Therefore, neurotoxicity is closely connected with human health. For decades, results showed similar phenotypical neurotoxicity in various laboratory animals, including dogs, cats, guinea pigs, rabbits, and rodents when repeatedly exposed to ACR levels ranging between 0.5 and 50 mg/kg/day. These neurological disorders may be caused by covalent adduct formation between highly nucleophilic cysteine and ACR at the active location of the presynaptic neuron. This process deactivates neurons and impacts neurotransmitter transfer, leading to neurotoxicity. Moreover, oxidative stress serves as a biochemical and physiological activation signal and is, directly and indirectly, related to the neurotoxicity caused by ACR. Although the potential molecular mechanism reported in recent years as underlying ACR-related neurotoxicity is multifaceted, a complete characterization and summary of the comprehensive mechanical system and its impact are still required. The aim of this study was to investigate The Mechanism of Acrylamide-Induced Neurotoxicity.
Methods: This review study has been written by The Mechanism of Acrylamide-Induced Neurotoxicity from scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
Results: Acrylamide is a small-molecule hydrophilic substance. It is absorbed via the gastrointestinal tracts of humans and animals and passively diffused to the entire body. ACR can also pass through the blood-brain barrier to directly exert its toxic effect on the nervous system. ACR follows two main metabolic pathways in the body. Briefly, an enzymatic reaction occurs when catalyzed by the cytochrome P450 enzyme system, CYP2E1, converting ACR into glycidamide (GA). Studies have found that GA can combine with purine bases on deoxyribonucleic acid (DNA) molecules to form DNA adducts, inhibit the release of neurotransmitters, cause nerve terminal degeneration, damage nerve structures, and display distinct cumulative effects. In addition, the ability of GA to form Hb and DNA adducts is more significant than ACR. Therefore, it is believed that this pathway is the main route of ACR-induced neurotoxicity. (2) ACR undergoes biotransformation and is catalyzed by glutathione S-transferase in the liver, combining with glutathione to generate N-acetyl-S-cysteine. It is further degraded into mercapturic ACR acids, which are excreted in the urine. This pathway is mainly responsible for ACR detoxification. Glutathione consumption reduces antioxidant levels, leading to excessive active oxygen accumulation and causing oxidative stress and neurotoxicity. Various reviews elaborate on the metabolic pathways of ACR. Those published by Koszucka et al. Rifai et al., and Fang et al. are recommended for more details.
Conclusion: Acrylamide (ACR), a potential neurotoxin, is produced by the Maillard reaction between reducing sugars and free amino acids during food processing. Over the past decade, the neurotoxicity of ACR has caused increasing concern, prompting many related studies.