Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules - LaftamBio, Federal University of Pampa - Campus Itaqui, 97650-000 Itaqui, RS, Brazil; Postgraduate Program in Biochemistry, Federal University of Pampa - Campus Uruguaiana, 97508-000 Uruguaiana, RS, Brazil.
Graduate Program in Food Technology, Federal Technological University of Paraná - Campus Campo Mourão, 87301-006 Campo Mourão, PR, Brazil.
Comp Biochem Physiol C Toxicol Pharmacol. 2024 Nov;285:109998. doi: 10.1016/j.cbpc.2024.109998. Epub 2024 Aug 4.
Neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), are characterized by persistent changes in communication and social interaction, as well as restricted and stereotyped patterns of behavior. The complex etiology of these disorders possibly combines the effects of multiple genes and environmental factors. Hence, exposure to insecticides such as imidacloprid (IMI) has been used to replicate the changes observed in these disorders. Lutein is known for its anti-inflammatory and antioxidant properties and is associated with neuroprotective effects. Therefore, the aim of this study was to evaluate the protective effect of lutein-loaded nanoparticles, along with their mechanisms of action, on Drosophila melanogaster offspring exposed to IMI-induced damage. To simulate the neurodevelopmental disorder model, flies were exposed to a diet containing IMI for 7 days. Posteriorly, their offspring were exposed to a diet containing lutein-loaded nanoparticles for a period of 24 h, and male and female flies were subjected to behavioral and biochemical evaluations. Treatment with lutein-loaded nanoparticles reversed the parameters of hyperactivity, aggressiveness, social interaction, repetitive movements, and anxiety in the offspring of flies exposed to IMI. It also protected markers of oxidative stress and cell viability, in addition to preventing the reduction of Nrf2 and Shank3 immunoreactivity. These results demonstrate that the damage induced by exposure to IMI was restored through treatment with lutein-loaded nanoparticles, elucidating lutein's mechanisms of action as a therapeutic agent, which, after further studies, can become a co-adjuvant in the treatment of neurodevelopmental disorders, such as ASD and ADHD.
神经发育障碍，如自闭症谱系障碍（ASD）和注意缺陷多动障碍（ADHD），其特征是沟通和社交互动持续变化，以及行为受限和刻板。这些疾病的复杂病因可能结合了多种基因和环境因素的影响。因此，接触像吡虫啉（IMI）这样的杀虫剂已被用于复制这些疾病中观察到的变化。叶黄素具有抗炎和抗氧化特性，并与神经保护作用相关。因此，本研究旨在评估叶黄素纳米载体制剂的保护作用及其作用机制，以研究其对暴露于 IMI 诱导损伤的黑腹果蝇后代的影响。为了模拟神经发育障碍模型，将果蝇暴露于含有 IMI 的饮食中 7 天。随后，它们的后代暴露于含有叶黄素纳米载体制剂的饮食中 24 小时，并对雄性和雌性果蝇进行行为和生化评估。用叶黄素纳米载体制剂处理可逆转暴露于 IMI 的果蝇后代的多动、攻击性、社交互动、重复运动和焦虑参数。它还保护了氧化应激和细胞活力的标志物，防止了 Nrf2 和 Shank3 免疫反应性的降低。这些结果表明，通过用叶黄素纳米载体制剂处理，可以恢复暴露于 IMI 所引起的损伤，阐明了叶黄素作为治疗剂的作用机制，在进一步研究后，它可能成为 ASD 和 ADHD 等神经发育障碍治疗的辅助药物。
