Quinoxaline, a Bioactive Compound Abundant in Marine Mangroves, Attenuates Acrylamide Induced Neurotoxicity in Zebrafish via Antioxidant, Anti-Inflammatory and Anti-Apoptotic Mechanisms

Background

Acrylamide, a widespread dietary and industrial contaminant, is a known neurotoxicant that promotes oxidative stress, inflammation, and neurodegeneration. Identifying effective neuroprotective agents is critical for counteracting its harmful effects.

Objectives

This study aimed to investigate the neuroprotective potential of quinoxaline, a heterocyclic compound with antioxidant properties, against acrylamide-induced neurotoxicity in adult zebrafish (Danio rerio).

Materials and Methods

Adult zebrafish were exposed to acrylamide to induce neurotoxicity, followed by quinoxaline treatment. Behavioral assays were performed to evaluate locomotor and cognitive function. Biochemical analyses quantified oxidative stress and inflammatory markers, including Superoxide Dismutase (SOD), Catalase (CAT), Lactate Dehydrogenase (LDH), Myeloperoxidase (MPO), Nitric Oxide (NO) and Glutathione (GSH). Histopathological examinations assessed neuronal integrity, while qRT-PCR evaluated the expression of stress-related genes (MPO and HSP-70).

Results

Acrylamide exposure caused significant motor and cognitive impairment, decreased SOD and CAT activity and increased LDH, MPO, NO and GSH levels, reflecting oxidative stress, nitrosative stress and inflammation. Quinoxaline treatment restored antioxidant enzyme activity, reduced pro-inflammatory markers and ameliorated behavioral deficits. Histological analysis showed preserved neuronal structures in quinoxaline-treated groups. Additionally, quinoxaline downregulated MPO and HSP-70 expression, confirming its protective role.

Conclusion

Quinoxaline demonstrated significant neuroprotective efficacy against acrylamide-induced toxicity by restoring redox balance, reducing inflammation and maintaining neuronal integrity. These findings highlight quinoxaline as a promising therapeutic candidate for managing acrylamide-induced neurotoxicity and related neurodegenerative disorders.