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芹黄素-C通过调节雄性大鼠的Akt/GSK-3β和Wnt-4/β-连环蛋白信号通路改善阿霉素诱导的肝毒性。

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

作者信息

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

机构信息

Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Department of Basic Medical Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al Bahah, Saudi Arabia.

出版信息

Front Mol Biosci. 2024 Dec 2;11:1507786. doi: 10.3389/fmolb.2024.1507786. eCollection 2024.

DOI:10.3389/fmolb.2024.1507786
PMID:39687571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11646862/
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. 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.

摘要

背景

用于癌症治疗的阿霉素（DOX）药物会引起各种不良反应，包括肝毒性。天然来源的成分在减轻化疗引起的毒性方面已显示出有前景的效果。本研究探讨了燕麦酰胺-C（AVN-C）治疗对DOX诱导的肝毒性大鼠的影响。

方法

使用AutoDock Vina进行分子对接研究。使用Pro Tox-III服务器对AVN-C和DOX进行毒性预测。将4组，每组10只雄性Sprague-Dawley大鼠：第1组（Gp1）作为阴性对照，第2组腹腔注射AVN-C（10mg/kg），第3组每周腹腔注射DOX（4mg/kg），持续1个月，第4组接受与第3组相同剂量的DOX和与第2组相同剂量的AVN-C。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治疗通过恢复生化改变、增强抗氧化活性、减轻炎症以及调节雄性大鼠的Akt/GSK-3β和Wnt-4/β-连环蛋白信号通路，显著改善了DOX诱导的大鼠肝毒性。

结论

本研究首次证明了AVN-C治疗对雄性大鼠DOX诱导的肝损伤具有治疗作用。因此，AVN-C可能对DOX治疗引起的肝毒性有显著的缓解作用。这些发现表明，AVN-C可能潜在地减轻与基于DOX的化疗相关的肝毒性。

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