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Therapeutic effect of bismuth subsalicylate in a propionic acid-induced autism model
Kubilay Doğan Kılıç1,2, Burak Çakar3, Yiğit Uyanıkgil4,5
1Department of Histology and Embryology, Faculty of Medicine, Ege University, İzmir, Türkiye. kubilay.dogan.kilic@ege.edu.tr.
Abstract:
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.
Insights
Bismuth subsalicylate (BSS) effectively reduced neuroinflammation and oxidative stress in a rat model of autism spectrum disorder (ASD). This treatment improved behavioral deficits, suggesting BSS
Area of Science:
- Neuroscience
- Pharmacology
- Autism Spectrum Disorders Research
Background:
- Neuroinflammation and oxidative stress, driven by reactive oxygen species in macrophages and microglia, are implicated in autism spectrum disorder (ASD) pathophysiology.
- This damaging cycle involves neuronal dysfunction, cell loss, and behavioral impairments, exacerbated by pro-inflammatory mediators released by activated microglia.
- Bismuth subsalicylate (BSS) possesses known anti-inflammatory and antioxidant properties, indicating potential therapeutic value in neurodegenerative conditions.
Purpose of the Study:
- To investigate the efficacy of Bismuth subsalicylate (BSS) in mitigating neuroinflammation and oxidative stress in a propionic acid (PPA)-induced rat model of autism.
- To assess the impact of BSS treatment on behavioral abnormalities associated with the PPA-induced autism-like phenotype.
- To evaluate the neuroprotective effects of BSS by examining biochemical and histological markers in brain tissues.
Main Methods:
- Thirty male Wistar albino rats were used, with an autism-like phenotype induced by intraperitoneal administration of propionic acid (PPA).
- Rats were divided into three groups: normal control, PPA + saline, and PPA + BSS, with treatments administered for 15 days.
- Behavioral tests (sociability, open field, passive avoidance) and biochemical/histological analyses of brain tissues were conducted.
Main Results:
- PPA administration significantly increased oxidative stress and inflammation markers (malondialdehyde, TNF-α, IL-17) compared to controls.
- BSS treatment markedly reduced these inflammatory and oxidative markers, indicating suppression of the damaging cycle.
- Histological analysis showed reduced glial activation and improved neuronal preservation in BSS-treated rats, alongside significant improvements in social interaction, exploration, and memory.
Conclusions:
- Bismuth subsalicylate (BSS) demonstrates significant neuroprotective effects in a PPA-induced autism model by attenuating oxidative stress and neuroinflammation.
- BSS treatment ameliorates behavioral deficits related to social interaction, exploration, and memory in this model.
- These findings suggest BSS holds therapeutic potential for managing aspects of autism spectrum disorders characterized by neuroinflammation and oxidative damage.
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