Salubrious effects of proanthocyanidins on behavioral phenotypes and DNA repair deficiency in the BTBR mouse model of autism

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Saudi Pharmaceutical Journal Pub Date : 2024-10-13 DOI:10.1016/j.jsps.2024.102187
Abdulelah F. Alhusain , Mohamed A. Mahmoud , Hussain N. Alhamami , Saad Ebrahim Alobid , Mushtaq A. Ansari , Sheikh F. Ahmad , Ahmed Nadeem , Saleh A. Bakheet , Gamaleldin I. Harisa , Sabry M. Attia
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Abstract

Autism is a neurodevelopmental disorder distinguished by impaired social interaction and repetitive behaviors. Global estimates indicate that autism affects approximately 1.6% of children, with the condition progressively becoming more prevalent over time. Despite noteworthy progress in autism research, the condition remains untreatable. This serves as a driving force for scientists to explore new approaches to disease management. Autism is linked to elevated levels of oxidative stress and disturbances in the DNA repair mechanism, which may potentially play a role in its comorbidities development. The current investigation aimed to evaluate the beneficial effect of the naturally occurring flavonoid proanthocyanidins on the behavioral characteristics and repair efficacy of autistic BTBR mice. Moreover, the mechanisms responsible for these effects were clarified. The present findings indicate that repeated administration of proanthocyanidins effectively reduces altered behavior in BTBR animals without altering motor function. Proanthocyanidins decreased oxidative DNA strand breaks and accelerated the rate of DNA repair in autistic animals, as evaluated by the modified comet test. In addition, proanthocyanidins reduced the elevated oxidative stress and recovered the disrupted DNA repair mechanism in the autistic animals by decreasing the expressions of Gadd45a and Parp1 levels and enhancing the expressions of Ogg1, P53, and Xrcc1 genes. This indicates that proanthocyanidins have significant potential as a new therapeutic strategy for alleviating autistic features.
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原花青素对自闭症 BTBR 小鼠模型的行为表型和 DNA 修复缺陷的有益影响
自闭症是一种神经发育障碍,主要表现为社交互动障碍和重复行为。据估计,全球约有 1.6% 的儿童患有自闭症,而且随着时间的推移,发病率会逐渐升高。尽管自闭症研究取得了显著进展,但这种疾病仍然无法治疗。这促使科学家们探索新的疾病治疗方法。自闭症与氧化应激水平升高和 DNA 修复机制紊乱有关,这可能是自闭症合并症发展的潜在因素。目前的研究旨在评估天然类黄酮原花青素对自闭症 BTBR 小鼠行为特征和修复功效的有益影响。此外,还阐明了产生这些影响的机制。目前的研究结果表明,反复服用原花青素可有效减少 BTBR 动物的行为改变,而不会改变其运动功能。根据改良彗星试验的评估,原花青素可减少自闭症动物的氧化 DNA 链断裂,加快 DNA 修复速度。此外,原花青素通过降低 Gadd45a 和 Parp1 的表达水平,提高 Ogg1、P53 和 Xrcc1 基因的表达水平,减少了自闭症动物体内升高的氧化应激,恢复了被破坏的 DNA 修复机制。这表明,原花青素作为一种新的治疗策略,在缓解自闭症特征方面具有巨大潜力。
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来源期刊
Saudi Pharmaceutical Journal
Saudi Pharmaceutical Journal PHARMACOLOGY & PHARMACY-
CiteScore
6.10
自引率
2.40%
发文量
194
审稿时长
67 days
期刊介绍: The Saudi Pharmaceutical Journal (SPJ) is the official journal of the Saudi Pharmaceutical Society (SPS) publishing high quality clinically oriented submissions which encompass the various disciplines of pharmaceutical sciences and related subjects. SPJ publishes 8 issues per year by the Saudi Pharmaceutical Society, with the cooperation of the College of Pharmacy, King Saud University.
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