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 Algarza, Arwa Ishaq A Khayyat, Luluah Saleh Alshaygy, Karim Samy El-Said
{"title":"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","authors":"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 Algarza, Arwa Ishaq A Khayyat, Luluah Saleh Alshaygy, Karim Samy El-Said","doi":"10.3389/fmolb.2024.1507786","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>AutoDock Vina was used for the molecular docking investigations. <i>In silico</i> 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1507786"},"PeriodicalIF":3.9000,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646862/pdf/","citationCount":"0","resultStr":"{\"title\":\"Avenanthramide-C ameliorate doxorubicin-induced hepatotoxicity via modulating Akt/GSK-3β and Wnt-4/β-Catenin pathways in male rats.\",\"authors\":\"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 Algarza, Arwa Ishaq A Khayyat, Luluah Saleh Alshaygy, Karim Samy El-Said\",\"doi\":\"10.3389/fmolb.2024.1507786\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>AutoDock Vina was used for the molecular docking investigations. <i>In silico</i> 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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. 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Avenanthramide-C ameliorate doxorubicin-induced hepatotoxicity via modulating Akt/GSK-3β and Wnt-4/β-Catenin pathways in male rats.
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.
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.
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