Kılıç Kubilay Doğan, Çakar Burak, Uyanıkgil Yiğit, Koenhemsi Lora, Güneş Berzah, Eroğlu Ebru, Erbaş Oytun
Department of Histology and Embryology, Faculty of Medicine, Ege University, İzmir, Türkiye.
Museum Für Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Berlin, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 15. doi: 10.1007/s00210-025-04255-z.
Inflammation-induced oxidative stress in macrophages and microglia is associated with excessive production of reactive oxygen species, initiating a damaging cycle of neuroinflammation and cellular injury. These processes are significant contributors to the pathophysiology of autism spectrum disorders, which involve neuronal dysfunction, cell loss, and behavioral impairments. Under conditions of oxidative stress, activated microglia release pro-inflammatory mediators, further intensifying neuronal damage. Bismuth subsalicylate (BSS), a compound with well-documented anti-inflammatory and antioxidant properties, has shown potential in mitigating such neurodegenerative processes. This study aimed to evaluate the effects of BSS in reducing neuroinflammation and oxidative stress in a propionic acid (PPA)-induced autism model, alongside its impact on behavioral outcomes. The study utilized 30 male Wistar albino rats, with PPA administered intraperitoneally at 250 mg/kg/day for 5 days to induce an autism-like phenotype. Rats were divided into three groups: Group 1 (Normal control, n = 10); Group 2 (PPA + saline, PPAS, n = 10); and Group 3 (PPA + BSS, PPAB, n = 10). Treatments were administered for 15 days. Behavioral performance was assessed through three-chamber sociability, open field, and passive avoidance learning tests, followed by biochemical and histological evaluations of brain tissues. Biochemical analysis revealed a significant increase in malondialdehyde, tumor necrosis factor-alpha, and interleukin-17 levels in the PPAS group, indicating heightened oxidative stress and inflammation. Treatment notably reduced these markers, suggesting its efficacy in mitigating oxidative damage and inflammatory responses. Immunohistochemical results demonstrated reduced glial activation and enhanced neuronal preservation in the hippocampal and cerebellar regions of treated rats. Additionally, behavioral impairments in social interaction, exploration, and memory were significantly improved with BSS therapy. These results suggest that BSS may confer neuroprotective effects through attenuation of oxidative stress and neuroinflammation, potentially contributing to improved neuronal function and behavioral performance in a PPA-induced autism model.
巨噬细胞和小胶质细胞中炎症诱导的氧化应激与活性氧的过量产生有关，从而引发神经炎症和细胞损伤的破坏性循环。这些过程是自闭症谱系障碍病理生理学的重要因素，自闭症谱系障碍涉及神经元功能障碍、细胞丢失和行为障碍。在氧化应激条件下，活化的小胶质细胞释放促炎介质，进一步加剧神经元损伤。碱式水杨酸铋（BSS）是一种具有充分文献记载的抗炎和抗氧化特性的化合物，已显示出减轻此类神经退行性过程的潜力。本研究旨在评估BSS在丙酸（PPA）诱导的自闭症模型中减少神经炎症和氧化应激的效果，以及其对行为结果的影响。该研究使用了30只雄性Wistar白化大鼠，以250mg/kg/天的剂量腹腔注射PPA，持续5天以诱导自闭症样表型。大鼠被分为三组：第1组（正常对照组，n = 10）；第2组（PPA + 生理盐水，PPAS，n = 10）；第3组（PPA + BSS，PPAB，n = 10）。治疗持续15天。通过三室社交性、旷场和被动回避学习测试评估行为表现，随后对脑组织进行生化和组织学评估。生化分析显示，PPAS组中丙二醛、肿瘤坏死因子-α和白细胞介素-17水平显著升高，表明氧化应激和炎症加剧。治疗显著降低了这些标志物，表明其在减轻氧化损伤和炎症反应方面的功效。免疫组织化学结果显示，治疗大鼠海马和小脑区域的胶质细胞活化减少，神经元保存增强。此外，BSS治疗显著改善了社交互动、探索和记忆方面的行为障碍。这些结果表明，BSS可能通过减轻氧化应激和神经炎症发挥神经保护作用，可能有助于改善PPA诱导的自闭症模型中的神经元功能和行为表现。
