Avenanthramide-C ameliorate doxorubicin-induced hepatotoxicity via modulating Akt/GSK-3β and Wnt-4/β-Catenin pathways in male rats.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Frontiers in Molecular Biosciences Pub Date : 2024-12-02 eCollection Date: 2024-01-01 DOI:10.3389/fmolb.2024.1507786

Maha Abdullah Alwaili, Amal S Abu-Almakarem, Salwa Aljohani, Sahar Abdulrahman Alkhodair, Maha M Al-Bazi, Thamir M Eid, Jehan Alamri, Maysa A Mobasher, Norah K Algarzae, Arwa Ishaq A Khayyat, Luluah Saleh Alshaygy, Karim Samy El-Said

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Abstract

Background: Doxorubicin (DOX) drugs used in cancer treatment can cause various adverse effects, including hepatotoxicity. Natural-derived constituents have shown promising effects in alleviating chemotherapy-induced toxicities. This study addressed the effect of Avenanthramides-C (AVN-C) treatment in rats with DOX-indued hepatotoxicity.

Methods: AutoDock Vina was used for the molecular docking investigations. In silico toxicity prediction for AVN-C and DOX was performed using the Pro Tox-III server. Four groups of ten male Sprague-Dawley rats were created: Group 1 (Gp1) served as a negative control, Gp2 received an intraperitoneal (i.p.) injection of AVN-C (10 mg/kg), Gp3 received an i.p. dose of DOX (4 mg/kg) weekly for a month, and Gp4 received the same dose of DOX as G3 and AVN-C as G2. Histopathological, molecular, and biochemical analyses were conducted 1 month later.

Results: The study showed that treatment with AVN-C significantly ameliorated DOX-induced hepatotoxicity in rats by restoring biochemical alterations, boosting antioxidant activity, reducing inflammation, and modulating the Akt/GSK-3β and Wnt-4/β-Catenin signaling pathways in male rats.

Conclusion: This study is the first to demonstrate the therapeutic effects of AVN-C therapy on DOX-induced liver damage in male rats. Therefore, AVN-C could have a pronounced palliative effect on the hepatotoxicity caused by DOX treatment. These findings suggest that AVN-C could potentially alleviate the hepatotoxicity associated with DOX-based chemotherapy.

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金刚烷胺-C通过调节雄性大鼠的Akt/GSK-3β和Wnt-4/β-Catenin通路改善多柔比星诱导的肝毒性

背景：多柔比星（DOX）药物用于癌症治疗可引起各种不良反应，包括肝毒性。天然来源的成分在减轻化疗引起的毒性方面显示出有希望的效果。本研究探讨了avenanthramide - c （AVN-C）对dox致肝毒性大鼠的治疗作用。方法：采用AutoDock Vina进行分子对接研究。使用Pro x- iii服务器进行AVN-C和DOX的硅毒性预测。将雄性sd大鼠分为4组，每组10只：1组（Gp1）为阴性对照，Gp2腹腔注射AVN-C (10 mg/kg)， Gp3腹腔注射DOX (4 mg/kg)，连续1个月，Gp4与G3、AVN-C分别给予相同剂量的DOX。1个月后进行组织病理学、分子和生化分析。结果：研究表明，AVN-C通过恢复雄性大鼠的生化改变、增强抗氧化活性、减轻炎症、调节Akt/GSK-3β和Wnt-4/β-Catenin信号通路，显著改善dox诱导的大鼠肝毒性。结论：本研究首次证实了AVN-C对dox诱导的雄性大鼠肝损伤的治疗作用。因此，AVN-C可能对DOX治疗引起的肝毒性具有明显的缓解作用。这些发现表明，AVN-C可能潜在地减轻与dox为基础的化疗相关的肝毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.