Amelioration of acrylamide induced neurotoxicity by benzo[b]thiophene analogs via glutathione redox dynamics in zebrafish larvae

Acrylamide is a thermal process contaminant, which gets global attention due to its neurotoxic nature and its omnipresence in carbohydrate-rich foods. Chronic exposure to acrylamide leads to neuronal deterioration and motor dysfunction. Acrylamide could severely affect the antioxidant defense system, especially in the developing brain leading to premature neurological disorders. Acrylamide forms adduct in presynaptic neurons leading to neuroinflammation which is also a factor to consider. In this present study, we have explored whether our benzo [b]thiophene analogs, 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen2-yl) propan-1-one hydrate (EP) with antioxidant activity, could inhibit the acrylamide-induced neurotoxicitylike behavior in zebrafish larvae. The experiment was set up to expose 3 days post fertilized (dpf) larvae to acrylamide (0.75 mM) for 3 days with or without compounds (80 mu M). Locomotion behavioral analysis, antioxidants, glutathione, and acetylcholineesterase activity in the head region were analyzed after one day of the experimental procedure. We witnessed a restoration effect on glutathione redox dynamics. Since glutathione plays a crucial role in the detoxification of acrylamide, it is necessary to maintain the glutathione redox cycle to eliminate acrylamide from the body. BP and EP reduced the pro-inflammatory transcript in the head, which correlates with the reduction in oxidative stress. Finally, BP and EP showed a positive effect on synaptic vesicle cycling transcript and partially restores the motor neuron response to stimuli. Findings in this study showed the ability of compound BP and EP possess therapeutic value in oxidative stress-associated neurological disorders.

Automated summary

This study demonstrates the therapeutic potential of compounds BP and EP in oxidative stress-associated neurological disorders. The experiment shows that these compounds can restore glutathione redox dynamics, reduce oxidative stress and neuroinflammation, and partially restore the normal function of motor neurons.