Protective Effect of Sulfur-Containing Heterocyclic Analogs Against Acrylamide-Induced Behavioral and Biochemical Alterations in Zebrafish

Acrylamide (ACR) is a water-soluble monomer with broad consumer applications, even in foods due to thermal processes. Acute exposure to ACR may lead to neurotoxic effects such as ataxia and skeletal muscle weakness in humans and experimental animals. Oxidative stress is the primary pathway in ACR toxicity; therefore, this study aimed to evaluate the possible protective effect of benzo[b]thiophene analogs as an antioxidant drug for ACR poisoning. For this purpose, adult zebrafish were chosen as the experimental model considering the 3Rs of research. Hydroxyl containing benzo[b]thiophene analogs, 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP) were injected via intraperitoneal (i.p.) route at an effective dose of 5 mg/kg one hour before the exposure of ACR (0.75 mM) for three days. ACR fish showed aberrant socio-behavior with low exploration, tight circling, negative scototaxis, disrupted aggression, and tight shoaling. These results indicated depression comorbid and anxiety-like phenotype. BP and EP partially reduced the aberrant socio-behavior. BP and EP elevated the antioxidant defense and reduced the oxidative damage in the brain caused by ACR. Cellular and tissular alterations caused by ACR were visualized through histopathological study. BP and EP administration reduced and repaired the cellular changes via the antioxidant mechanism. BP and EP altered the axonal growth and regeneration gene and synaptic vesicle cycle gene expression necessary for neurotransmission. This combined gain-of-function of redox mechanism at molecular, cellular, and tissular levels explains the behavioral improvement at the organismal level of the organization.