Haridevamuthu B, Manjunathan Tamilvelan, Boopathi Seenivasan, Almutairi Mikhlid H, Almutairi Bader O, Kumar Thipramalai Thankappan Ajith, Guru Ajay, Gopinath Pushparathinam, Arockiaraj Jesu
Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India.
Department of Chemistry, Faculty of Engineering and Technology, Jain University, Bangalore, 562112, India.
Mol Neurobiol. 2025 Mar;62(3):2781-2800. doi: 10.1007/s12035-024-04440-w. Epub 2024 Aug 20.
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.
丙烯酰胺（ACR）是一种水溶性单体，在消费领域有广泛应用，甚至在经过热加工的食品中也存在。人类和实验动物急性接触ACR可能会导致神经毒性效应，如共济失调和骨骼肌无力。氧化应激是ACR毒性的主要途径；因此，本研究旨在评估苯并[b]噻吩类似物作为ACR中毒抗氧化药物的可能保护作用。为此，考虑到研究的3R原则，选择成年斑马鱼作为实验模型。在暴露于ACR（0.75 mM）三天前一小时，通过腹腔注射（i.p.）途径，以5 mg/kg的有效剂量注射含羟基的苯并[b]噻吩类似物1-(3-羟基苯并[b]噻吩-2-基)乙酮（BP）和1-(3-羟基苯并[b]噻吩-2-基)丙-1-酮水合物（EP）。ACR处理的鱼表现出异常的社会行为，探索性低、紧密盘旋、负趋暗性、攻击性破坏和紧密聚群。这些结果表明存在抑郁共病和焦虑样表型。BP和EP部分减轻了异常的社会行为。BP和EP提高了抗氧化防御能力，并减少了ACR对大脑造成的氧化损伤。通过组织病理学研究观察到ACR引起的细胞和组织改变。BP和EP给药通过抗氧化机制减少并修复了细胞变化。BP和EP改变了神经传递所需的轴突生长和再生基因以及突触小泡循环基因的表达。这种在分子、细胞和组织水平上氧化还原机制的综合功能增益解释了在生物体组织水平上行为的改善。
